Usher syndrome
Encyclopedia
Usher syndrome is a relatively rare genetic disorder
that is a leading cause of deafblindness
and that is associated with a mutation in any one of 10 gene
s. Other names for Usher syndrome include Hallgren syndrome, Usher-Hallgren syndrome, rp
-dysacusis syndrome and dystrophia retinae dysacusis syndrome. Usher syndrome is incurable at present; however, using gene therapy
to replace the missing gene, researchers have succeeded in reversing one form of the disease in knockout mice
.
is characterized by deafness and a gradual vision loss. The hearing loss is associated with a defective inner ear
, whereas the vision loss is associated with retinitis pigmentosa
(RP), a degeneration of the retinal cells. Usually, the rod cell
s of the retina
are affected first, leading to early night blindness and the gradual loss of peripheral vision
. In other cases, there is early degeneration of the cone cell
s in the macula
, leading to a loss of central acuity
. In some cases, the fovea
l vision is spared, leading to "doughnut vision"; central and peripheral vision are intact, but there is an annulus
around the central region in which vision is impaired
.
Usher syndrome has three clinical subtypes, denoted as I, II and III. People with Usher I are born profoundly deaf, and begin to lose their vision
in the first decade of life. They also exhibit balance difficulties
and learn to walk slowly as children, due to problems in their vestibular system
. People with Usher II are not born deaf, but do have hearing loss. They do not seem to have noticeable problems with balance; they also begin to lose their vision later (in the second decade of life) and may preserve some vision even into middle age. People with Usher syndrome III are not born deaf, but experience a gradual loss of their hearing and vision; they may or may not have balance difficulties.
Usher syndrome is a variable condition; the degree of severity is not tightly linked to whether it is Usher 1, 2 or 3. For example, someone with Type 3 may be unaffected in childhood but go on to develop a profound hearing loss and a very significant loss of sight by early to mid-adulthood. Similarly, someone with Type 1, who is therefore profoundly deaf from birth, may keep good central vision until the sixth decade of life, or even beyond. People with Type 3, who have useful hearing with a hearing aid, can experience a wide range of severity of the RP. Some may maintain good reading vision into their sixties, while others cannot see to read while still in their forties.
Usher syndrome I and II are associated with a mutation in any one of six or three different gene
s, respectively, whereas only one mutation has been linked with Usher III. Since Usher syndrome is inherited in an autosomal recessive pattern, both males and females are equally likely to inherit Usher syndrome. Consanguinity
of the parents is a risk factor. Children of parents who both are carriers of the same mutation have a one fourth chance of inheriting the condition and children of such parents who are unaffected have a two thirds chance of being carriers. Children of parents where only one parent is a carrier have a no chance of having the disease but have a one half chance of being a carrier. First recognized in the 19th century, Usher syndrome was the first condition to demonstrate that phenotype
s could be inherited in tandem; deafness and blindness
are inherited together, but not separately. Animal models of this human disease (such as knockout mice
and zebrafish) have been developed recently to study the effects of these gene mutations and to test potential cures for Usher syndrome.
, who examined the pathology
and transmission
of this illness in 1914 on the basis of 69 cases. However, it was first described in 1858 by Albrecht von Gräfe
, a pioneer of modern ophthalmology
. He reported the case of a deaf patient with retinitis pigmentosa
, who had two brothers with the same symptoms. Three years later, one of his students, Richard Liebreich
, examined the population of Berlin for disease pattern of deafness with retinitis pigmentosa. Liebreich noted that Usher syndrome is recessive, since the cases of blind-deafness combinations occurred particularly in the siblings of blood-related marriages or in families with patients in different generations. His observations supplied the first proofs for the coupled transmission of blindness and deafness, since no isolated cases of either could be found in the family trees.
Usher syndrome is responsible for the majority of deaf-blindness. The word syndrome
means that multiple symptoms occur together, in this case, deafness and blindness. It occurs in roughly 1 person in 23,000 in the United States
, 1 in 28,000 in Norway and 1 in 12,500 in Germany. People with Usher syndrome represent roughly one-sixth of people with retinitis pigmentosa
.
Usher syndrome is inherited in an autosomal recessive pattern. "Recessive" means that both parents must contribute an appropriate gene
for the syndrome to appear, and "autosomal" means that the gene is not carried on one of the sex chromosome
s (X or Y), but rather on one of the 22 other pairs. (See the article on human genetics
for more details.)
The progressive blindness of Usher syndrome results from retinitis pigmentosa
. The photoreceptor cells usually start to degenerate from the outer periphery to the center of the retina
including the macula
. The degeneration is usually first noticed as night blindness (nyctalopia
); peripheral vision is gradually lost, restricting the visual field (tunnel vision
), which generally progresses to complete blindness. The qualifier pigmentosa reflects the fact that clumps of pigment may be visible by an ophthalmoscope in advanced stages of degeneration.
Although Usher syndrome has been classified clinically in several ways, the prevailing approach is to classify it into three clinical sub-types called Usher I, II and III in order of decreasing severity of deafness. Usher I and II are the more common forms; the fraction of people with Usher III is significant only in a few specific areas, such as Finland
and Birmingham
. As described below, these clinical subtypes may be further subdivided by the particular gene mutated; people with Usher I and II may have any one of six and three genes mutated, respectively, whereas only one gene has been associated with Usher III. The function of these genes is poorly understood as of yet. The hearing impairment associated with Usher syndrome is better understood: damaged hair cells in the cochlea
of the inner ear
inhibit electrical impulses from reaching the brain.
owing to problems in the vestibular system
. Babies with Usher I are usually slow to develop motor skills such as walking. Worldwide, the estimated prevalence of Usher syndrome type I is 3 to 6 per 100,000 people in the general population.
Usher syndrome type I can be caused by mutations in any one of several different genes: CDH23
, MYO7A
, PCDH15
, USH1C
, and USH1G
. These genes function in the development and maintenance of inner ear
structures such as hair cell
s (stereocilia
), which transmit sound
and motion
signals to the brain
. Alterations in these genes can cause an inability to maintain balance (vestibular dysfunction) and hearing loss. The genes also play a role in the development and stability of the retina
by influencing the structure and function of both the rod photoreceptor cells and supporting cells called the retinal pigmented epithelium. Mutations that affect the normal function of these genes can result in retinitis pigmentosa
and vision loss.
Type I has been found to be more common in people of Ashkenazi Jewish ancestry (central and eastern European) and in the French-Acadian populations (Louisiana).
Usher syndrome type II may be caused by mutations in any of three different genes: USH2A
, GPR98
and DFNB31
. The protein encoded by the USH2A gene, usherin, is located in the supportive tissue in the inner ear
and retina
. Usherin is critical for the proper development and maintenance of these structures, which may help explain its role in hearing and vision loss. The location and function of the other two proteins are not yet known.
, but it has been noted rarely in a few other ethnic groups.
Mutations in only one gene, the CLRN1
gene, have been linked to Usher syndrome type III. The CLRN1 gene encodes Clarin-1, a protein that is important for the development and maintenance of the inner ear and retina. However, the protein's function in these structures, and how its mutation causes hearing and vision loss, is poorly understood as yet.
The simplest approach to diagnosing Usher syndrome is to test for the characteristic chromosomal mutations. An alternative approach is electroretinography
(ERG), although this is often disfavored for children, since its discomfort can also make the results unreliable. Parental consanguinity is a significant factor in diagnosis. Usher syndrome I may be indicated if the child is profoundly deaf from birth and especially slow in walking.
Thirteen other syndromes may exhibit signs similar to Usher syndrome, including Alport syndrome
, Alstrom syndrome
, Bardet-Biedl syndrome
, Cockayne syndrome
, spondyloepiphyseal dysplasia congenita
, Flynn-Aird syndrome, Friedreich ataxia, Hurler syndrome
(MPS-1), Kearns-Sayre syndrome
(CPEO), Norrie syndrome, osteopetrosis
(Albers-Schonberg disease), Refsum's disease
(phytanic acid storage disease), and Zellweger syndrome
(cerebro-hepato-renal syndrome).
Several gene
s have been associated with Usher syndrome using linkage analysis of patient families (Table 1) and DNA sequencing
of the identified loci
. A mutation in any one of these genes is likely to result in Usher syndrome. The clinical subtypes Usher I and II are associated with mutations in any one of six (USH1B-G) and three (USH2A,C-D) genes, respectively, whereas only one gene, USH3A, has been linked to Usher III so far. Two other genes, USH1A and USH2B, were initially associated with Usher syndrome, but USH2B has not been verified and USH1A was incorrectly determined and does not exist. Research in this area is ongoing.
Using interaction analysis techniques it could be shown that the identified gene products interact with one another in one or more larger protein complex
es. If one of the components is missing, this protein complex cannot fulfill its function in the living cell
and it probably comes to the degeneration
the same. The function of this protein complex has been suggested to participate in the signal transduction
or in the cell adhesion
of sensory cells.
that adds the proper protein back ("gene replacement") may alleviate it, provided that the added protein becomes functional. Recent studies of mouse models
have shown that one form of the disease — that associated with a mutation in myosin
VIIa — can be alleviated by replacing the mutant gene
using a lentivirus
. However, some of the mutated genes associated with Usher syndrome encode
very large protein
s — most notably, the USH2A
and GPR98
protein
s, which have roughly 6000 amino-acid
residues. Gene replacement therapy for such large proteins may be difficult.
in November 2007. After graduating from the University of Michigan
with excellent marks, Alexander went on to Columbia University
, where she earned two master's degrees in public health and clinical social work. Rebecca is an active member of her community working with various charities in NYC. Rebecca's dedication as an active member of her community was most notably recognized when she was selected as a "Community Hero" to run with the Olympic Torch for the 1996 Atlanta Olympic Games in honor of her volunteer work for Project Open Hand, a non-profit organization delivering meals to people living with HIV/AIDS in the San Francisco Bay Area. Rebecca received her psychodynamic psychotherapy training through the American Institute of Psychoanalysis. She currently works in private practice specializing in the treatment of mood and anxiety disorders, eating disorders, addictions, disability, and trauma. While currently facilitating group seminars for the Foundation Fighting Blindness
during national conferences, Rebecca is also in the process of launching the Usher III Initiative, a non-profit organization dedicated to science and research that seek to find a cure for Usher III. Rebecca teaches indoor cycling/spin classes with a strong following at select gyms in New York City. She was featured on NBC's Today Show on March 20, 2009 which has been nominated for an Emmy award in September 2010. She is the sister of NBC News National Correspondent Peter Alexander.
Christine "Coco" Roschaert is a well-known person with Usher syndrome. She has published video blogs at Youtube, and recently was the kick-off speaker for the Deaf Awareness Week at the University of Vermont
. In 2006, she graduated with a degree in Communication Sciences from Gallaudet University
; there, she was a hunger striker in the 2006 protest organized by the Gallaudet United Now Movement
. Roschaert is now in Nigeria
founding the first deafblind program in that country.
A web-community, UsherLife, of people with Usher syndrome was founded on 1 February 2005 by Nick Sturley. Although centered on Great Britain
, it offers resources to all people with Usher syndrome. The organization is hosting regular get-togethers in England, such as the Usher Hood Pub in Nottingham and a trip to Brighton pier. Other people with Usher syndrome have posted videos about their lives and condition on YouTube
, most notably Ginny Paja-Nyholm. In October 2007, Candice, a mom living in Texas, began blogging about her two daughters, Jasmine and Rebecca; Rebecca has Usher syndrome I.
Catherine Fischer has written a well-received autobiography of growing up with Usher syndrome in Louisiana, entitled Orchid of the Bayou. Similarly, Vendon Wright has written two books describing his life with Usher syndrome, I was blind but now I can see and Through my eyes. Louise Boardman has also written a short book called My son has Usher's Syndrome.
Christian Markovic, an artist living with Usher syndrome, runs a company, Fuzzy Wuzzy Designs.
Spencer Tracy
's son John was a well-known person with Usher syndrome who lived a full life. The John Tracy Clinic
was founded in 1942 by his mother Louise to offer free help to parents of hearing-impaired infants and preschool children.
Jacob Desormeaux, son of horse-racing jockey Kent Desormeaux
, suffers from Usher syndrome. Jacob was born deaf and is progressively going blind. Kent dedicated his race in the Belmont Stakes
, which would give him and his horse Big Brown
the Triple Crown, to his son Jacob. The family has started an organization to raise funds and awareness of the disease. Usher syndrome is disproportionately common among the Cajuns of south Louisiana, such as Desormeaux and Fischer, because of a genetic mutation among early French Acadian
settlers in Nova Scotia
.
DNA helix co-discoverer and Nobel laureate James D. Watson
has homozygous USH1B mutations, according to his published genome. It is not clear why he did not develop the syndrome. This lack of genetic penetrance argues that expression of the phenotype
of Usher syndrome may be more complex than originally assumed.
The Israeli “Nalaga’at” (do touch) Deaf-blind Acting Ensemble consists of 11 deaf-blind actors, most of whom diagnosed with Usher syndrome. The theater group has put on several productions and appeared both locally in Israel and abroad in London and Broadway.
Genetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
that is a leading cause of deafblindness
Deafblindness
Deafblindness is the condition of little or no useful sight and little or no useful hearing. Educationally, individuals are considered to be deafblind when the combination of their hearing and vision loss causes such severe communication and other developmental and educational needs that they...
and that is associated with a mutation in any one of 10 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
s. Other names for Usher syndrome include Hallgren syndrome, Usher-Hallgren syndrome, rp
Retinitis pigmentosa
Retinitis pigmentosa is a group of genetic eye conditions that leads to incurable blindness. In the progression of symptoms for RP, night blindness generally precedes tunnel vision by years or even decades. Many people with RP do not become legally blind until their 40s or 50s and retain some...
-dysacusis syndrome and dystrophia retinae dysacusis syndrome. Usher syndrome is incurable at present; however, using gene therapy
Gene therapy
Gene therapy is the insertion, alteration, or removal of genes within an individual's cells and biological tissues to treat disease. It is a technique for correcting defective genes that are responsible for disease development...
to replace the missing gene, researchers have succeeded in reversing one form of the disease in knockout mice
Knockout mouse
A knockout mouse is a genetically engineered mouse in which researchers have inactivated, or "knocked out," an existing gene by replacing it or disrupting it with an artificial piece of DNA...
.
Characteristcs
This syndromeSyndrome
In medicine and psychology, a syndrome is the association of several clinically recognizable features, signs , symptoms , phenomena or characteristics that often occur together, so that the presence of one or more features alerts the physician to the possible presence of the others...
is characterized by deafness and a gradual vision loss. The hearing loss is associated with a defective inner ear
Inner ear
The inner ear is the innermost part of the vertebrate ear. In mammals, it consists of the bony labyrinth, a hollow cavity in the temporal bone of the skull with a system of passages comprising two main functional parts:...
, whereas the vision loss is associated with retinitis pigmentosa
Retinitis pigmentosa
Retinitis pigmentosa is a group of genetic eye conditions that leads to incurable blindness. In the progression of symptoms for RP, night blindness generally precedes tunnel vision by years or even decades. Many people with RP do not become legally blind until their 40s or 50s and retain some...
(RP), a degeneration of the retinal cells. Usually, the rod cell
Rod cell
Rod cells, or rods, are photoreceptor cells in the retina of the eye that can function in less intense light than can the other type of visual photoreceptor, cone cells. Named for their cylindrical shape, rods are concentrated at the outer edges of the retina and are used in peripheral vision. On...
s of the retina
Retina
The vertebrate retina is a light-sensitive tissue lining the inner surface of the eye. The optics of the eye create an image of the visual world on the retina, which serves much the same function as the film in a camera. Light striking the retina initiates a cascade of chemical and electrical...
are affected first, leading to early night blindness and the gradual loss of peripheral vision
Peripheral vision
Peripheral vision is a part of vision that occurs outside the very center of gaze. There is a broad set of non-central points in the field of view that is included in the notion of peripheral vision...
. In other cases, there is early degeneration of the cone cell
Cone cell
Cone cells, or cones, are photoreceptor cells in the retina of the eye that are responsible for color vision; they function best in relatively bright light, as opposed to rod cells that work better in dim light. If the retina is exposed to an intense visual stimulus, a negative afterimage will be...
s in the macula
Macula
The macula or macula lutea is an oval-shaped highly pigmented yellow spot near the center of the retina of the human eye. It has a diameter of around 5 mm and is often histologically defined as having two or more layers of ganglion cells...
, leading to a loss of central acuity
Visual acuity
Visual acuity is acuteness or clearness of vision, which is dependent on the sharpness of the retinal focus within the eye and the sensitivity of the interpretative faculty of the brain....
. In some cases, the fovea
Fovea
The fovea centralis, also generally known as the fovea , is a part of the eye, located in the center of the macula region of the retina....
l vision is spared, leading to "doughnut vision"; central and peripheral vision are intact, but there is an annulus
Annulus (mathematics)
In mathematics, an annulus is a ring-shaped geometric figure, or more generally, a term used to name a ring-shaped object. Or, it is the area between two concentric circles...
around the central region in which vision is impaired
Visual impairment
Visual impairment is vision loss to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive...
.
Usher syndrome has three clinical subtypes, denoted as I, II and III. People with Usher I are born profoundly deaf, and begin to lose their vision
Visual perception
Visual perception is the ability to interpret information and surroundings from the effects of visible light reaching the eye. The resulting perception is also known as eyesight, sight, or vision...
in the first decade of life. They also exhibit balance difficulties
Balance disorder
A balance disorder is a disturbance that causes an individual to feel unsteady, for example when standing or walking. It may be accompanied by feelings of giddiness or wooziness, or having a sensation of movement, spinning, or floating...
and learn to walk slowly as children, due to problems in their vestibular system
Vestibular system
The vestibular system, which contributes to balance in most mammals and to the sense of spatial orientation, is the sensory system that provides the leading contribution about movement and sense of balance. Together with the cochlea, a part of the auditory system, it constitutes the labyrinth of...
. People with Usher II are not born deaf, but do have hearing loss. They do not seem to have noticeable problems with balance; they also begin to lose their vision later (in the second decade of life) and may preserve some vision even into middle age. People with Usher syndrome III are not born deaf, but experience a gradual loss of their hearing and vision; they may or may not have balance difficulties.
Usher syndrome is a variable condition; the degree of severity is not tightly linked to whether it is Usher 1, 2 or 3. For example, someone with Type 3 may be unaffected in childhood but go on to develop a profound hearing loss and a very significant loss of sight by early to mid-adulthood. Similarly, someone with Type 1, who is therefore profoundly deaf from birth, may keep good central vision until the sixth decade of life, or even beyond. People with Type 3, who have useful hearing with a hearing aid, can experience a wide range of severity of the RP. Some may maintain good reading vision into their sixties, while others cannot see to read while still in their forties.
Usher syndrome I and II are associated with a mutation in any one of six or three different gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
s, respectively, whereas only one mutation has been linked with Usher III. Since Usher syndrome is inherited in an autosomal recessive pattern, both males and females are equally likely to inherit Usher syndrome. Consanguinity
Consanguinity
Consanguinity refers to the property of being from the same kinship as another person. In that respect, consanguinity is the quality of being descended from the same ancestor as another person...
of the parents is a risk factor. Children of parents who both are carriers of the same mutation have a one fourth chance of inheriting the condition and children of such parents who are unaffected have a two thirds chance of being carriers. Children of parents where only one parent is a carrier have a no chance of having the disease but have a one half chance of being a carrier. First recognized in the 19th century, Usher syndrome was the first condition to demonstrate that phenotype
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
s could be inherited in tandem; deafness and blindness
Blindness
Blindness is the condition of lacking visual perception due to physiological or neurological factors.Various scales have been developed to describe the extent of vision loss and define blindness...
are inherited together, but not separately. Animal models of this human disease (such as knockout mice
Knockout mouse
A knockout mouse is a genetically engineered mouse in which researchers have inactivated, or "knocked out," an existing gene by replacing it or disrupting it with an artificial piece of DNA...
and zebrafish) have been developed recently to study the effects of these gene mutations and to test potential cures for Usher syndrome.
History
Usher syndrome is named after the British ophthalmologist Charles UsherCharles Usher
Charles Howard Usher was a Scottish ophthalmologist from Edinburgh. He studied medicine at St. Thomas Hospital in London, and after receiving his doctorate in 1891, he remained at St. Thomas, working under Edward Nettleship...
, who examined the pathology
Pathology
Pathology is the precise study and diagnosis of disease. The word pathology is from Ancient Greek , pathos, "feeling, suffering"; and , -logia, "the study of". Pathologization, to pathologize, refers to the process of defining a condition or behavior as pathological, e.g. pathological gambling....
and transmission
Transmission (medicine)
In medicine and biology, transmission is the passing of a communicable disease from an infected host individual or group to a conspecific individual or group, regardless of whether the other individual was previously infected...
of this illness in 1914 on the basis of 69 cases. However, it was first described in 1858 by Albrecht von Gräfe
Albrecht von Gräfe
Friedrich Wilhelm Ernst Albrecht von Graefe was a pioneering German ophthalmologist. Graefe was born in Finkenheerd, Brandenburg, the son of Karl Ferdinand von Graefe...
, a pioneer of modern ophthalmology
Ophthalmology
Ophthalmology is the branch of medicine that deals with the anatomy, physiology and diseases of the eye. An ophthalmologist is a specialist in medical and surgical eye problems...
. He reported the case of a deaf patient with retinitis pigmentosa
Retinitis pigmentosa
Retinitis pigmentosa is a group of genetic eye conditions that leads to incurable blindness. In the progression of symptoms for RP, night blindness generally precedes tunnel vision by years or even decades. Many people with RP do not become legally blind until their 40s or 50s and retain some...
, who had two brothers with the same symptoms. Three years later, one of his students, Richard Liebreich
Richard Liebreich
Richard Liebreich was a German ophthalmologist and physiologist who was a native of Königsberg.In 1853 he earned his doctorate at Halle, and from 1854 until 1862 was an assistant to Albrecht von Graefe in Berlin. He subsequently practiced medicine in Paris and London , where he was head of...
, examined the population of Berlin for disease pattern of deafness with retinitis pigmentosa. Liebreich noted that Usher syndrome is recessive, since the cases of blind-deafness combinations occurred particularly in the siblings of blood-related marriages or in families with patients in different generations. His observations supplied the first proofs for the coupled transmission of blindness and deafness, since no isolated cases of either could be found in the family trees.
Symptoms and subtypes
Syndrome
In medicine and psychology, a syndrome is the association of several clinically recognizable features, signs , symptoms , phenomena or characteristics that often occur together, so that the presence of one or more features alerts the physician to the possible presence of the others...
means that multiple symptoms occur together, in this case, deafness and blindness. It occurs in roughly 1 person in 23,000 in the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
, 1 in 28,000 in Norway and 1 in 12,500 in Germany. People with Usher syndrome represent roughly one-sixth of people with retinitis pigmentosa
Retinitis pigmentosa
Retinitis pigmentosa is a group of genetic eye conditions that leads to incurable blindness. In the progression of symptoms for RP, night blindness generally precedes tunnel vision by years or even decades. Many people with RP do not become legally blind until their 40s or 50s and retain some...
.
Usher syndrome is inherited in an autosomal recessive pattern. "Recessive" means that both parents must contribute an appropriate gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
for the syndrome to appear, and "autosomal" means that the gene is not carried on one of the sex chromosome
XY sex-determination system
The XY sex-determination system is the sex-determination system found in humans, most other mammals, some insects and some plants . In this system, females have two of the same kind of sex chromosome , and are called the homogametic sex. Males have two distinct sex chromosomes , and are called...
s (X or Y), but rather on one of the 22 other pairs. (See the article on human genetics
Human genetics
Human genetics describes the study of inheritance as it occurs in human beings. Human genetics encompasses a variety of overlapping fields including: classical genetics, cytogenetics, molecular genetics, biochemical genetics, genomics, population genetics, developmental genetics, clinical genetics,...
for more details.)
The progressive blindness of Usher syndrome results from retinitis pigmentosa
Retinitis pigmentosa
Retinitis pigmentosa is a group of genetic eye conditions that leads to incurable blindness. In the progression of symptoms for RP, night blindness generally precedes tunnel vision by years or even decades. Many people with RP do not become legally blind until their 40s or 50s and retain some...
. The photoreceptor cells usually start to degenerate from the outer periphery to the center of the retina
Retina
The vertebrate retina is a light-sensitive tissue lining the inner surface of the eye. The optics of the eye create an image of the visual world on the retina, which serves much the same function as the film in a camera. Light striking the retina initiates a cascade of chemical and electrical...
including the macula
Macula
The macula or macula lutea is an oval-shaped highly pigmented yellow spot near the center of the retina of the human eye. It has a diameter of around 5 mm and is often histologically defined as having two or more layers of ganglion cells...
. The degeneration is usually first noticed as night blindness (nyctalopia
Nyctalopia
Nyctalopia is a condition making it difficult or impossible to see in relatively low light. It is a symptom of several eye diseases. Night blindness may exist from birth, or be caused by injury or malnutrition...
); peripheral vision is gradually lost, restricting the visual field (tunnel vision
Tunnel vision
Tunnel vision is the loss of peripheral vision with retention of central vision, resulting in a constricted circular tunnel-like field of vision.- Medical / biological causes :Tunnel vision can be caused by:...
), which generally progresses to complete blindness. The qualifier pigmentosa reflects the fact that clumps of pigment may be visible by an ophthalmoscope in advanced stages of degeneration.
Although Usher syndrome has been classified clinically in several ways, the prevailing approach is to classify it into three clinical sub-types called Usher I, II and III in order of decreasing severity of deafness. Usher I and II are the more common forms; the fraction of people with Usher III is significant only in a few specific areas, such as Finland
Finland
Finland , officially the Republic of Finland, is a Nordic country situated in the Fennoscandian region of Northern Europe. It is bordered by Sweden in the west, Norway in the north and Russia in the east, while Estonia lies to its south across the Gulf of Finland.Around 5.4 million people reside...
and Birmingham
Birmingham
Birmingham is a city and metropolitan borough in the West Midlands of England. It is the most populous British city outside the capital London, with a population of 1,036,900 , and lies at the heart of the West Midlands conurbation, the second most populous urban area in the United Kingdom with a...
. As described below, these clinical subtypes may be further subdivided by the particular gene mutated; people with Usher I and II may have any one of six and three genes mutated, respectively, whereas only one gene has been associated with Usher III. The function of these genes is poorly understood as of yet. The hearing impairment associated with Usher syndrome is better understood: damaged hair cells in the cochlea
Cochlea
The cochlea is the auditory portion of the inner ear. It is a spiral-shaped cavity in the bony labyrinth, making 2.5 turns around its axis, the modiolus....
of the inner ear
Inner ear
The inner ear is the innermost part of the vertebrate ear. In mammals, it consists of the bony labyrinth, a hollow cavity in the temporal bone of the skull with a system of passages comprising two main functional parts:...
inhibit electrical impulses from reaching the brain.
Usher syndrome I
People with Usher I are usually born deaf and often have difficulties in maintaining their balanceBalance disorder
A balance disorder is a disturbance that causes an individual to feel unsteady, for example when standing or walking. It may be accompanied by feelings of giddiness or wooziness, or having a sensation of movement, spinning, or floating...
owing to problems in the vestibular system
Vestibular system
The vestibular system, which contributes to balance in most mammals and to the sense of spatial orientation, is the sensory system that provides the leading contribution about movement and sense of balance. Together with the cochlea, a part of the auditory system, it constitutes the labyrinth of...
. Babies with Usher I are usually slow to develop motor skills such as walking. Worldwide, the estimated prevalence of Usher syndrome type I is 3 to 6 per 100,000 people in the general population.
Usher syndrome type I can be caused by mutations in any one of several different genes: CDH23
CDH23
Cadherin-23 is a protein that in humans is encoded by the CDH23 gene.-Further reading:...
, MYO7A
MYO7A
Myosin VIIA is protein that in humans is encoded by the MYO7A gene. Myosin VIIA is a member of the unconventional myosin superfamily of proteins...
, PCDH15
PCDH15
Protocadherin-15 is a protein that in humans is encoded by the PCDH15 gene.-External Links:* -Further reading:...
, USH1C
USH1C
Harmonin is a protein that in humans is encoded by the USH1C gene.-External links:* -Further reading:...
, and USH1G
USH1G
Usher syndrome type-1G protein is a protein that in humans is encoded by the USH1G gene.-External Links:* -Further reading:...
. These genes function in the development and maintenance of inner ear
Inner ear
The inner ear is the innermost part of the vertebrate ear. In mammals, it consists of the bony labyrinth, a hollow cavity in the temporal bone of the skull with a system of passages comprising two main functional parts:...
structures such as hair cell
Hair cell
Hair cells are the sensory receptors of both the auditory system and the vestibular system in all vertebrates. In mammals, the auditory hair cells are located within the organ of Corti on a thin basilar membrane in the cochlea of the inner ear...
s (stereocilia
Stereocilia
In the inner ear, stereocilia are the mechanosensing organelles of hair cells, which respond to fluid motion in numerous types of animals for various functions, including hearing and balance. They are about 10–50 micrometers in length and share some similar features of microvilli...
), which transmit sound
Sound
Sound is a mechanical wave that is an oscillation of pressure transmitted through a solid, liquid, or gas, composed of frequencies within the range of hearing and of a level sufficiently strong to be heard, or the sensation stimulated in organs of hearing by such vibrations.-Propagation of...
and motion
Motion (physics)
In physics, motion is a change in position of an object with respect to time. Change in action is the result of an unbalanced force. Motion is typically described in terms of velocity, acceleration, displacement and time . An object's velocity cannot change unless it is acted upon by a force, as...
signals to the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
. Alterations in these genes can cause an inability to maintain balance (vestibular dysfunction) and hearing loss. The genes also play a role in the development and stability of the retina
Retina
The vertebrate retina is a light-sensitive tissue lining the inner surface of the eye. The optics of the eye create an image of the visual world on the retina, which serves much the same function as the film in a camera. Light striking the retina initiates a cascade of chemical and electrical...
by influencing the structure and function of both the rod photoreceptor cells and supporting cells called the retinal pigmented epithelium. Mutations that affect the normal function of these genes can result in retinitis pigmentosa
Retinitis pigmentosa
Retinitis pigmentosa is a group of genetic eye conditions that leads to incurable blindness. In the progression of symptoms for RP, night blindness generally precedes tunnel vision by years or even decades. Many people with RP do not become legally blind until their 40s or 50s and retain some...
and vision loss.
Type I has been found to be more common in people of Ashkenazi Jewish ancestry (central and eastern European) and in the French-Acadian populations (Louisiana).
Usher syndrome II
People with Usher II are generally hard-of-hearing rather than deaf, and their hearing does not degrade over time; moreover, they generally have a normal vestibular system. Usher syndrome type II occurs at least as frequently as type I, but because type II may be underdiagnosed or more difficult to detect, it could be up to three times as common as type I.Usher syndrome type II may be caused by mutations in any of three different genes: USH2A
USH2A
Usherin is a protein that in humans is encoded by the USH2A gene.-External Links:* -Further reading:...
, GPR98
GPR98
G protein-coupled receptor 98, also known as GPR98, is a human protein and gene.-External Links:* -Further reading:...
and DFNB31
DFNB31
Whirlin is a protein that in humans is encoded by the DFNB31 gene.-Further reading:...
. The protein encoded by the USH2A gene, usherin, is located in the supportive tissue in the inner ear
Inner ear
The inner ear is the innermost part of the vertebrate ear. In mammals, it consists of the bony labyrinth, a hollow cavity in the temporal bone of the skull with a system of passages comprising two main functional parts:...
and retina
Retina
The vertebrate retina is a light-sensitive tissue lining the inner surface of the eye. The optics of the eye create an image of the visual world on the retina, which serves much the same function as the film in a camera. Light striking the retina initiates a cascade of chemical and electrical...
. Usherin is critical for the proper development and maintenance of these structures, which may help explain its role in hearing and vision loss. The location and function of the other two proteins are not yet known.
Usher syndrome III
By contrast, people with Usher III experience a progressive loss of hearing and roughly half have vestibular dysfunction. The frequency of Usher syndrome type III is highest in the Finnish populationFinland
Finland , officially the Republic of Finland, is a Nordic country situated in the Fennoscandian region of Northern Europe. It is bordered by Sweden in the west, Norway in the north and Russia in the east, while Estonia lies to its south across the Gulf of Finland.Around 5.4 million people reside...
, but it has been noted rarely in a few other ethnic groups.
Mutations in only one gene, the CLRN1
CLRN1
Clarin-1 is a protein that in humans is encoded by the CLRN1 gene.-External links:*...
gene, have been linked to Usher syndrome type III. The CLRN1 gene encodes Clarin-1, a protein that is important for the development and maintenance of the inner ear and retina. However, the protein's function in these structures, and how its mutation causes hearing and vision loss, is poorly understood as yet.
Differential diagnosis
Since Usher syndrome is incurable at present, it is helpful to diagnose children well before they develop the characteristic night blindness. Some preliminary studies have suggested that as many as 10% of congenitally deaf children may have Usher syndrome. However, a mis-diagnosis can have bad consequences.The simplest approach to diagnosing Usher syndrome is to test for the characteristic chromosomal mutations. An alternative approach is electroretinography
Electroretinography
Electroretinography measures the electrical responses of various cell types in the retina, including the photoreceptors , inner retinal cells , and the ganglion cells. Electrodes are usually placed on the cornea and the skin near the eye, although it is possible to record the ERG from skin electrodes...
(ERG), although this is often disfavored for children, since its discomfort can also make the results unreliable. Parental consanguinity is a significant factor in diagnosis. Usher syndrome I may be indicated if the child is profoundly deaf from birth and especially slow in walking.
Thirteen other syndromes may exhibit signs similar to Usher syndrome, including Alport syndrome
Alport syndrome
Alport syndrome or hereditary nephritis is a genetic disorder characterized by glomerulonephritis, endstage kidney disease, and hearing loss. Alport syndrome can also affect the eyes . The presence of blood in the urine is almost always found in this condition.It was first identified in a British...
, Alstrom syndrome
Alstrom syndrome
Alström syndrome is a rare genetic disorder caused by mutations in the gene ALMS1. It is among the rarest genetic disorders in the world, as currently it has only 266 reported cases in medical literature and over 501 known cases in 47 countries. It was first described by Carl-Henry Alström in...
, Bardet-Biedl syndrome
Bardet-Biedl syndrome
The Bardet–Biedl syndrome is a ciliopathic human genetic disorder that produces many effects and affects many body systems. It is characterized principally by obesity, retinitis pigmentosa, polydactyly, mental retardation, hypogonadism, and renal failure in some cases.-Summary of the...
, Cockayne syndrome
Cockayne syndrome
Cockayne syndrome is a rare autosomal recessive, congenital disorder characterized by growth failure, impaired development of the nervous system, abnormal sensitivity to sunlight , and premature aging...
, spondyloepiphyseal dysplasia congenita
Spondyloepiphyseal dysplasia congenita
Spondyloepiphyseal dysplasia congenita is a rare disorder of bone growth that results in dwarfism, characteristic skeletal abnormalities, and occasionally problems with vision and hearing...
, Flynn-Aird syndrome, Friedreich ataxia, Hurler syndrome
Hurler syndrome
Hurler syndrome, also known as mucopolysaccharidosis type I , Hurler's disease, also gargoylism, is a genetic disorder that results in the buildup of glycosaminoglycans due to a deficiency of alpha-L iduronidase, an enzyme responsible for the degradation of mucopolysaccharides in lysosomes...
(MPS-1), Kearns-Sayre syndrome
Kearns-Sayre syndrome
Kearns–Sayre syndrome also known as oculocraniosomatic disease or Oculocraniosomatic neuromuscular disease with ragged red fibers is a mitochondrial myopathy with a typical onset before 20 years of age...
(CPEO), Norrie syndrome, osteopetrosis
Osteopetrosis
Osteopetrosis, literally "stone bone", also known as marble bone disease and Albers-Schonberg disease is an extremely rare inherited disorder whereby the bones harden, becoming denser, in contrast to more prevalent conditions like osteoporosis, in which the bones become less dense and more brittle,...
(Albers-Schonberg disease), Refsum's disease
Refsum's disease
Refsum disease, also known as classic or adult Refsum disease, heredopathia atactica polyneuritiformis, phytanic acid oxidase deficiency and phytanic acid storage disease, is an autosomal recessive neurological disease that results from the over-accumulation of phytanic acid in cells and tissues...
(phytanic acid storage disease), and Zellweger syndrome
Zellweger syndrome
Zellweger syndrome, also called cerebrohepatorenal syndrome is a rare, congenital disorder, characterized by the reduction or absence of functional peroxisomes in the cells of an individual. It is one of a family of disorders called leukodystrophies...
(cerebro-hepato-renal syndrome).
Genes associated with Usher syndrome
| Type | Freq | Gene locus | Gene | Protein | Function | Size (AA) | UniProt | OMIM |
|---|---|---|---|---|---|---|---|---|
| USH1B | 39–55% | 11q13.5 | MYO7A MYO7A Myosin VIIA is protein that in humans is encoded by the MYO7A gene. Myosin VIIA is a member of the unconventional myosin superfamily of proteins... |
Myosin Myosin Myosins comprise a family of ATP-dependent motor proteins and are best known for their role in muscle contraction and their involvement in a wide range of other eukaryotic motility processes. They are responsible for actin-based motility. The term was originally used to describe a group of similar... VIIA |
Motor protein | 2215 | ||
| USH1C | 6–7% | 11p15.1-p14 | USH1C USH1C Harmonin is a protein that in humans is encoded by the USH1C gene.-External links:* -Further reading:... |
Harmonin Usher 1C Usher 1C is a human gene. Recessive alleles of this gene are responsible for type 1C Usher syndrome and nonsyndromic deafness.The official name of the gene Usher 1C is “Usher syndrome 1C .”... |
PDZ-domain protein PDZ domain The PDZ domain is a common structural domain of 80-90 amino-acids found in the signaling proteins of bacteria, yeast, plants, viruses and animals... |
552 | ||
| USH1D | 19–35% | 10q21-q22 | CDH23 CDH23 Cadherin-23 is a protein that in humans is encoded by the CDH23 gene.-Further reading:... |
Cadherin 23 Cadherin Cadherins are a class of type-1 transmembrane proteins. They play important roles in cell adhesion, ensuring that cells within tissues are bound together. They are dependent on calcium ions to function, hence their name.The cadherin superfamily includes cadherins, protocadherins, desmogleins, and... |
Cell adhesion Cell adhesion Cellular adhesion is the binding of a cell to a surface, extracellular matrix or another cell using cell adhesion molecules such as selectins, integrins, and cadherins. Correct cellular adhesion is essential in maintaining multicellular structure... |
3354 | ||
| USH1E | rare | 21q21 | ? | ? | ? | ? | ? | |
| USH1F | 11–19% | 10q11.2-q21 | PCDH15 PCDH15 Protocadherin-15 is a protein that in humans is encoded by the PCDH15 gene.-External Links:* -Further reading:... |
Protocadherin 15 Cadherin Cadherins are a class of type-1 transmembrane proteins. They play important roles in cell adhesion, ensuring that cells within tissues are bound together. They are dependent on calcium ions to function, hence their name.The cadherin superfamily includes cadherins, protocadherins, desmogleins, and... |
Cell adhesion Cell adhesion Cellular adhesion is the binding of a cell to a surface, extracellular matrix or another cell using cell adhesion molecules such as selectins, integrins, and cadherins. Correct cellular adhesion is essential in maintaining multicellular structure... |
1955 | ||
| USH1G | 7% | 17q24-q25 | USH1G USH1G Usher syndrome type-1G protein is a protein that in humans is encoded by the USH1G gene.-External Links:* -Further reading:... |
SANS | Scaffold protein Scaffold protein In biology, scaffold proteins are crucial regulators of many key signaling pathways. Although scaffolds are not strictly defined in function, they are known to interact and/or bind with multiple members of a signaling pathway, tethering them into complexes... |
461 | ||
| USH2A | 80% | 1q41 | USH2A USH2A Usherin is a protein that in humans is encoded by the USH2A gene.-External Links:* -Further reading:... |
Usherin | Transmembrane linkage | 5202 | ||
| USH2C | 15% | 5q14.3-q21.1 | GPR98 GPR98 G protein-coupled receptor 98, also known as GPR98, is a human protein and gene.-External Links:* -Further reading:... |
VLGR1b | Very large GPCR | 6307 | ||
| USH2D | 5% | 9q32-q34 | DFNB31 DFNB31 Whirlin is a protein that in humans is encoded by the DFNB31 gene.-Further reading:... |
Whirlin | PDZ-domain protein PDZ domain The PDZ domain is a common structural domain of 80-90 amino-acids found in the signaling proteins of bacteria, yeast, plants, viruses and animals... |
907 | ||
| USH3A | 100% | 3q21-q25 | CLRN1 CLRN1 Clarin-1 is a protein that in humans is encoded by the CLRN1 gene.-External links:*... |
Clarin-1 | Synaptic shaping | 232 |
Several gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
s have been associated with Usher syndrome using linkage analysis of patient families (Table 1) and DNA sequencing
DNA sequencing
DNA sequencing includes several methods and technologies that are used for determining the order of the nucleotide bases—adenine, guanine, cytosine, and thymine—in a molecule of DNA....
of the identified loci
Locus (genetics)
In the fields of genetics and genetic computation, a locus is the specific location of a gene or DNA sequence on a chromosome. A variant of the DNA sequence at a given locus is called an allele. The ordered list of loci known for a particular genome is called a genetic map...
. A mutation in any one of these genes is likely to result in Usher syndrome. The clinical subtypes Usher I and II are associated with mutations in any one of six (USH1B-G) and three (USH2A,C-D) genes, respectively, whereas only one gene, USH3A, has been linked to Usher III so far. Two other genes, USH1A and USH2B, were initially associated with Usher syndrome, but USH2B has not been verified and USH1A was incorrectly determined and does not exist. Research in this area is ongoing.
Using interaction analysis techniques it could be shown that the identified gene products interact with one another in one or more larger protein complex
Protein complex
A multiprotein complex is a group of two or more associated polypeptide chains. If the different polypeptide chains contain different protein domain, the resulting multiprotein complex can have multiple catalytic functions...
es. If one of the components is missing, this protein complex cannot fulfill its function in the living cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
and it probably comes to the degeneration
Degeneration
The idea of degeneration had significant influence on science, art and politics from the 1850s to the 1950s. The social theory developed consequently from Charles Darwin's Theory of Evolution...
the same. The function of this protein complex has been suggested to participate in the signal transduction
Signal transduction
Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...
or in the cell adhesion
Cell adhesion
Cellular adhesion is the binding of a cell to a surface, extracellular matrix or another cell using cell adhesion molecules such as selectins, integrins, and cadherins. Correct cellular adhesion is essential in maintaining multicellular structure...
of sensory cells.
Prospects for gene therapy
Since Usher syndrome results from the loss of a gene, gene therapyGene therapy
Gene therapy is the insertion, alteration, or removal of genes within an individual's cells and biological tissues to treat disease. It is a technique for correcting defective genes that are responsible for disease development...
that adds the proper protein back ("gene replacement") may alleviate it, provided that the added protein becomes functional. Recent studies of mouse models
Knockout mouse
A knockout mouse is a genetically engineered mouse in which researchers have inactivated, or "knocked out," an existing gene by replacing it or disrupting it with an artificial piece of DNA...
have shown that one form of the disease — that associated with a mutation in myosin
Myosin
Myosins comprise a family of ATP-dependent motor proteins and are best known for their role in muscle contraction and their involvement in a wide range of other eukaryotic motility processes. They are responsible for actin-based motility. The term was originally used to describe a group of similar...
VIIa — can be alleviated by replacing the mutant gene
Gene therapy
Gene therapy is the insertion, alteration, or removal of genes within an individual's cells and biological tissues to treat disease. It is a technique for correcting defective genes that are responsible for disease development...
using a lentivirus
Lentivirus
Lentivirus is a genus of slow viruses of the Retroviridae family, characterized by a long incubation period...
. However, some of the mutated genes associated with Usher syndrome encode
Central dogma of molecular biology
The central dogma of molecular biology was first articulated by Francis Crick in 1958 and re-stated in a Nature paper published in 1970:In other words, the process of producing proteins is irreversible: a protein cannot be used to create DNA....
very large protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s — most notably, the USH2A
USH2A
Usherin is a protein that in humans is encoded by the USH2A gene.-External Links:* -Further reading:...
and GPR98
GPR98
G protein-coupled receptor 98, also known as GPR98, is a human protein and gene.-External Links:* -Further reading:...
protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s, which have roughly 6000 amino-acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
residues. Gene replacement therapy for such large proteins may be difficult.
Individual cases
A 31-year-old woman with Usher syndrome, Rebecca Alexander, was profiled in Marie ClaireMarie Claire
Marie Claire is a monthly women's magazine first published in France but also distributed in other countries with editions specific to them and in their languages. While each country shares its own special voice with its audience, the United States edition focuses on women around the world and...
in November 2007. After graduating from the University of Michigan
University of Michigan
The University of Michigan is a public research university located in Ann Arbor, Michigan in the United States. It is the state's oldest university and the flagship campus of the University of Michigan...
with excellent marks, Alexander went on to Columbia University
Columbia University
Columbia University in the City of New York is a private, Ivy League university in Manhattan, New York City. Columbia is the oldest institution of higher learning in the state of New York, the fifth oldest in the United States, and one of the country's nine Colonial Colleges founded before the...
, where she earned two master's degrees in public health and clinical social work. Rebecca is an active member of her community working with various charities in NYC. Rebecca's dedication as an active member of her community was most notably recognized when she was selected as a "Community Hero" to run with the Olympic Torch for the 1996 Atlanta Olympic Games in honor of her volunteer work for Project Open Hand, a non-profit organization delivering meals to people living with HIV/AIDS in the San Francisco Bay Area. Rebecca received her psychodynamic psychotherapy training through the American Institute of Psychoanalysis. She currently works in private practice specializing in the treatment of mood and anxiety disorders, eating disorders, addictions, disability, and trauma. While currently facilitating group seminars for the Foundation Fighting Blindness
Foundation Fighting Blindness
The mission of the Foundation Fighting Blindness is to fund research that will lead to preventions, treatments, and cures for retinal degenerative diseases including: retinitis pigmentosa, macular degeneration, Usher syndrome and Stargardt disease. These diseases affect more than 10 million...
during national conferences, Rebecca is also in the process of launching the Usher III Initiative, a non-profit organization dedicated to science and research that seek to find a cure for Usher III. Rebecca teaches indoor cycling/spin classes with a strong following at select gyms in New York City. She was featured on NBC's Today Show on March 20, 2009 which has been nominated for an Emmy award in September 2010. She is the sister of NBC News National Correspondent Peter Alexander.
Christine "Coco" Roschaert is a well-known person with Usher syndrome. She has published video blogs at Youtube, and recently was the kick-off speaker for the Deaf Awareness Week at the University of Vermont
University of Vermont
The University of Vermont comprises seven undergraduate schools, an honors college, a graduate college, and a college of medicine. The Honors College does not offer its own degrees; students in the Honors College concurrently enroll in one of the university's seven undergraduate colleges or...
. In 2006, she graduated with a degree in Communication Sciences from Gallaudet University
Gallaudet University
Gallaudet University is a federally-chartered university for the education of the deaf and hard of hearing, located in the District of Columbia, U.S...
; there, she was a hunger striker in the 2006 protest organized by the Gallaudet United Now Movement
Gallaudet United Now Movement
The Unity for Gallaudet Movement is a protest movement started by students, faculty and alumni of Gallaudet University and other sympathizers who do not support the nomination of Dr. Jane Fernandes as president of the university. I...
. Roschaert is now in Nigeria
Nigeria
Nigeria , officially the Federal Republic of Nigeria, is a federal constitutional republic comprising 36 states and its Federal Capital Territory, Abuja. The country is located in West Africa and shares land borders with the Republic of Benin in the west, Chad and Cameroon in the east, and Niger in...
founding the first deafblind program in that country.
A web-community, UsherLife, of people with Usher syndrome was founded on 1 February 2005 by Nick Sturley. Although centered on Great Britain
Great Britain
Great Britain or Britain is an island situated to the northwest of Continental Europe. It is the ninth largest island in the world, and the largest European island, as well as the largest of the British Isles...
, it offers resources to all people with Usher syndrome. The organization is hosting regular get-togethers in England, such as the Usher Hood Pub in Nottingham and a trip to Brighton pier. Other people with Usher syndrome have posted videos about their lives and condition on YouTube
YouTube
YouTube is a video-sharing website, created by three former PayPal employees in February 2005, on which users can upload, view and share videos....
, most notably Ginny Paja-Nyholm. In October 2007, Candice, a mom living in Texas, began blogging about her two daughters, Jasmine and Rebecca; Rebecca has Usher syndrome I.
Catherine Fischer has written a well-received autobiography of growing up with Usher syndrome in Louisiana, entitled Orchid of the Bayou. Similarly, Vendon Wright has written two books describing his life with Usher syndrome, I was blind but now I can see and Through my eyes. Louise Boardman has also written a short book called My son has Usher's Syndrome.
Christian Markovic, an artist living with Usher syndrome, runs a company, Fuzzy Wuzzy Designs.
Spencer Tracy
Spencer Tracy
Spencer Bonaventure Tracy was an American theatrical and film actor, who appeared in 75 films from 1930 to 1967. Tracy was one of the major stars of Hollywood's Golden Age, ranking among the top ten box office draws for almost every year from 1938 to 1951...
's son John was a well-known person with Usher syndrome who lived a full life. The John Tracy Clinic
John Tracy Clinic
John Tracy Clinic is a private, non-profit education center for infants and preschool children with hearing loss in Los Angeles, California, USA. It was founded by Louise Treadwell Tracy, wife of actor Spencer Tracy, in 1942. It provides free, parent-centered services worldwide...
was founded in 1942 by his mother Louise to offer free help to parents of hearing-impaired infants and preschool children.
Jacob Desormeaux, son of horse-racing jockey Kent Desormeaux
Kent Desormeaux
Kent Jason Desormeaux is an American thoroughbred horse racing Hall of Fame jockey who holds the U.S. record for most races won in a single year, 1989.-Brief biography:...
, suffers from Usher syndrome. Jacob was born deaf and is progressively going blind. Kent dedicated his race in the Belmont Stakes
Belmont Stakes
The Belmont Stakes is an American Grade I stakes Thoroughbred horse race held every June at Belmont Park in Elmont, New York. It is a 1.5-mile horse race, open to three year old Thoroughbreds. Colts and geldings carry a weight of 126 pounds ; fillies carry 121 pounds...
, which would give him and his horse Big Brown
Big Brown
Big Brown is a retired champion American Thoroughbred racehorse and winner of the 2008 Kentucky Derby and 2008 Preakness Stakes. Bred by Dr. Gary B. Knapp's Monticule Farms in Lexington, Kentucky, he won his first five race starts. He was sired by Grade III winner Boundary, a son of North American...
the Triple Crown, to his son Jacob. The family has started an organization to raise funds and awareness of the disease. Usher syndrome is disproportionately common among the Cajuns of south Louisiana, such as Desormeaux and Fischer, because of a genetic mutation among early French Acadian
Acadian
The Acadians are the descendants of the 17th-century French colonists who settled in Acadia . Acadia was a colony of New France...
settlers in Nova Scotia
Nova Scotia
Nova Scotia is one of Canada's three Maritime provinces and is the most populous province in Atlantic Canada. The name of the province is Latin for "New Scotland," but "Nova Scotia" is the recognized, English-language name of the province. The provincial capital is Halifax. Nova Scotia is the...
.
DNA helix co-discoverer and Nobel laureate James D. Watson
James D. Watson
James Dewey Watson is an American molecular biologist, geneticist, and zoologist, best known as one of the co-discoverers of the structure of DNA in 1953 with Francis Crick...
has homozygous USH1B mutations, according to his published genome. It is not clear why he did not develop the syndrome. This lack of genetic penetrance argues that expression of the phenotype
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
of Usher syndrome may be more complex than originally assumed.
The Israeli “Nalaga’at” (do touch) Deaf-blind Acting Ensemble consists of 11 deaf-blind actors, most of whom diagnosed with Usher syndrome. The theater group has put on several productions and appeared both locally in Israel and abroad in London and Broadway.
General information
- GeneReviews/NCBI/NIH/UW entry on Usher Syndrome Type I
- GeneReviews/NCBI/NIH/UW entry on Usher Syndrome Type II
- Usher syndrome in the Swedish Rare Disease Database
- General overview from the NIH
- Usher Syndrome Information from the National Institute on Deafness and Other Communication Disorders (NIDCD).
- Usher syndrome Information from Sense, a British organization for deafblind people
- Scientific review of Usher 1
- Scientific review of Usher 2
- Usher Syndrome Selected Topics - National Consortium On Deaf-Blindness
Resources
- Usher Syndrome Resource Guide from the National Eye Institute (NEI).
- Usher syndrome mailing list
- Boys Town National Research Hospital
- The Williams retinal Physiology Research Group, UCSD
- http://www.boystownhospital.org/Usher/information.asp
- http://www.boystownhospital.org/Usher/index.asp
- http://www.hearseehope.com
- http://usher-syndrome.org - The Coalition for Usher Syndrome Research