Achondrogenesis
Encyclopedia
Achondrogenesis is a number of disorders that are the most severe form of congenital chondrodysplasia (malformation of bone
s and cartilage
). These conditions are characterized by a small body, short limbs, and other skeletal abnormalities. As a result of their serious health problems, infants with achondrogenesis are usually born premature
ly, are stillborn
, or die shortly after birth from respiratory failure. Some infants, however, have lived for a while with intensive medical support.
Researchers have described at least three forms of achondrogenesis, designated as Achondrogenesis type 1A, achondrogenesis type 1B
and achondrogenesis type 2
. These types are distinguished by their signs and symptoms, inheritance pattern, and genetic cause. Other types of achondrogenesis may exist, but they have not been characterized or their cause is unknown.
Achondrogenesis type 1A is caused by a defect in the microtubules of the Golgi apparatus
. In mice, a nonsense mutation in the thyroid hormone receptor interactor 11 gene (Trip11), which encodes the Golgi microtubule-associated protein 210 (GMAP-210), resulted in defects similar to the human disease. When their DNA was sequenced, human patients with achondrogenesis type 1A also had loss-of-function mutations in GMAP-210. GMAP-210 moves proteins from the endoplasmic reticulum to the Golgi apparatus. Because of the defect, GMAP-210 is not able to move the proteins, and they remain in the endoplasmic reticulum, which swells up. The loss of Golgi apparatus function affects some cells, such as those responsible for forming bone and cartilage, more than others.
Achondrogenesis type 1B is caused by a similar mutation in SLC26A2, which encodes a sulfate transporter.
Bone
Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...
s and cartilage
Cartilage
Cartilage is a flexible connective tissue found in many areas in the bodies of humans and other animals, including the joints between bones, the rib cage, the ear, the nose, the elbow, the knee, the ankle, the bronchial tubes and the intervertebral discs...
). These conditions are characterized by a small body, short limbs, and other skeletal abnormalities. As a result of their serious health problems, infants with achondrogenesis are usually born premature
Premature
Premature can refer to:*Premature aging: see Senescence*Premature birth or prematurity: see Preterm birth*Premature ejaculation*Premature menopause*Premature stop codon: see Nonsense mutation*Premature ventricular contraction...
ly, are stillborn
Stillbirth
A stillbirth occurs when a fetus has died in the uterus. The Australian definition specifies that fetal death is termed a stillbirth after 20 weeks gestation or the fetus weighs more than . Once the fetus has died the mother still has contractions and remains undelivered. The term is often used in...
, or die shortly after birth from respiratory failure. Some infants, however, have lived for a while with intensive medical support.
Researchers have described at least three forms of achondrogenesis, designated as Achondrogenesis type 1A, achondrogenesis type 1B
Achondrogenesis type 1B
Achondrogenesis, type 1B is characterized by extremely short limbs, a narrow chest, and a prominent, rounded abdomen. The fingers and toes are short and the feet may be rotated inward...
and achondrogenesis type 2
Achondrogenesis type 2
Infants with achondrogenesis, type 2 have short arms and legs, a small chest with short ribs, and underdeveloped lungs. Achondrogenesis, type 2 is a subtype of collagenopathy, types II and XI. This condition is also associated with a lack of bone formation in the spine and pelvis...
. These types are distinguished by their signs and symptoms, inheritance pattern, and genetic cause. Other types of achondrogenesis may exist, but they have not been characterized or their cause is unknown.
Achondrogenesis type 1A is caused by a defect in the microtubules of the Golgi apparatus
Golgi apparatus
The Golgi apparatus is an organelle found in most eukaryotic cells. It was identified in 1898 by the Italian physician Camillo Golgi, after whom the Golgi apparatus is named....
. In mice, a nonsense mutation in the thyroid hormone receptor interactor 11 gene (Trip11), which encodes the Golgi microtubule-associated protein 210 (GMAP-210), resulted in defects similar to the human disease. When their DNA was sequenced, human patients with achondrogenesis type 1A also had loss-of-function mutations in GMAP-210. GMAP-210 moves proteins from the endoplasmic reticulum to the Golgi apparatus. Because of the defect, GMAP-210 is not able to move the proteins, and they remain in the endoplasmic reticulum, which swells up. The loss of Golgi apparatus function affects some cells, such as those responsible for forming bone and cartilage, more than others.
Achondrogenesis type 1B is caused by a similar mutation in SLC26A2, which encodes a sulfate transporter.