COL11A2

The COL11A2 gene provides instructions for making one component of type XI collagen, called the pro-alpha2(XI) chain. Type XI collagen adds structure and strength to the connective tissues that support the body's muscles, joints, organs, and skin. Type XI collagen is normally found in cartilage, a tough but flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears. Type XI collagen is also part of the clear gel that fills the eyeball (the vitreous), the inner ear, and the center portion of the discs between the vertebrae in the spine (nucleus pulposus).

To construct type XI collagen, the pro-alpha2(XI) chain combines with two other collagen chains (pro-alpha1(XI) and pro-alpha1(II)) to form a procollagen molecule. These triple-stranded, ropelike procollagen molecules are then processed by enzymes in the cell. Once processed, procollagen molecules leave the cell and arrange themselves into long, thin fibrils that link to one another (cross-link) in the spaces around cells. The cross-linkages result in the formation of very strong mature type XI collagen fibers.

Type XI collagen also helps maintain the spacing and diameter of type II collagen fibrils. Type II collagen is an important component of the eye and mature cartilage tissue. The size and arrangement of type II collagen fibrils are essential for the normal structure of these tissues.

nonsyndromic deafness - caused by mutations in the COL11A2 gene

Mutations in the COL11A2 gene cause a form of nonsyndromic deafness (hearing loss without related signs and symptoms affecting other parts of the body) called DFNA13. This type of deafness has been identified in two large families. In one family, a mutation replaces the amino acid arginine (a building block of proteins) with the amino acid cysteine at position 549 in the pro-alpha2(XI) chain of type XI collagen. This mutation is written as Arg549Cys. A second family has a mutation that substitutes the amino acid glutamic acid for the amino acid glycine at position 323 (written as Gly323Glu) in this protein. These mutations prevent the normal assembly of type XI collagen, which plays an important role in the structure and function of the inner ear.

otospondylomegaepiphyseal dysplasia - caused by mutations in the COL11A2 gene

Approximately 10 mutations in the COL11A2 gene have been found to cause otospondylomegaepiphyseal dysplasia (OSMED), a bone growth disorder. Most of these mutations result in a complete lack of pro-alpha2(XI) chains, which impairs the function of type XI collagen. Some mutations affect the production of the pro-alpha2(XI) chain and disrupt the assembly of type XI collagen. Type XI collagen is an important component of cartilage and other connective tissues, and its loss or impairment results in the characteristic signs and symptoms of OSMED.

Stickler syndrome - caused by mutations in the COL11A2 gene

Mutations in the COL11A2 gene can cause Stickler syndrome, a condition characterized by impaired skeletal development and hearing loss. COL11A2 mutations cause abnormal production of the pro-alpha2(XI) chain, part of type XI collagen. As a result, type XI collagen cannot function properly, causing the signs and symptoms of Stickler syndrome.

This type of Stickler syndrome is sometimes called the non-ocular type because it does not affect vision (unlike the other types of Stickler syndrome caused by mutations in other genes). The pro-alpha2(XI) chain is not found in the eyes and COL11A2 mutations do not affect vision. Instead, another type of collagen chain replaces pro-alpha2(XI) to form type XI collagen in the clear gel that fills the eyeball (the vitreous).

Weissenbacher-Zweymüller syndrome - caused by mutations in the COL11A2 gene

At least one mutation in the COL11A2 gene has been found to cause Weissenbacher-Zweymüller syndrome. This mutation replaces the amino acid glycine with the amino acid glutamic acid at position 955 in the collagen pro-alpha2(XI) chain (written as Gly955Glu). This mutation prevents collagen molecules from being assembled properly, which disrupts the structure of type XI collagen. These changes in type XI collagen result in the characteristic signs and symptoms of Weissenbacher-Zweymüller syndrome, including short stature, distinctive facial features, and occasionally, hearing loss.

other disorders - increased risk from variations of the COL11A2 gene

In some people, variations in the COL11A2 gene may increase the risk of developing osteoarthritis, a degenerative disease of joint cartilage. As a result of these genetic changes, incorrect amino acids are used in making the pro-alpha2(XI) chain of type XI collagen. The altered pro-alpha2(XI) chain may weaken collagen fibers, which could play a role in the erosion of cartilage in the joints, a characteristic feature of osteoarthritis.