Otoespondilomegaepifisaria dysplasia (Dysplasia otospondylomegaepiphyseal) - Gen COL11A2
The otospondilomegaepifisalia dysplasia (OSMED) is a skeletal disorder characterized by skeletal abnormalities, distinctive facial features and severe hearing loss. OSMED characteristics are similar to two skeletal abnormalities called Weissenbacher-Zweymüller syndrome and Type III Stickler syndrome.
Signs and symptoms associated with this disease may include short stature, enlarged joints, platyspondyly, joint pain, limited joint motion, arthritis, and severe hearing loss. Referring to the facial features of individuals affected, they may include bulging eyes, flattened nose bridge, upturned nose with a large round tip, and a small lower jaw. In addition, virtually all affected children are born with cleft palate. In individuals with this disease, skeletal characteristics tend to decrease during childhood, but other signs and symptoms such as hearing loss and joint pain persist into adulthood.
This process is due to mutations in the gene COL11A2 (collagen type XI alpha 2), located on the short arm of chromosome 6 (6p21.3). This gene encodes a component of type XI collagen, called pro-alpha2 chain (XI). Type XI collagen adds the structure and strength to the connective tissues of the body that support the muscles, joints, organs and skin. Type XI collagen is normally found in cartilage that makes up much of the skeleton in early development. Collagen type XI is also part of the vitreous, the inner ear and nucleus pulposus. Collagen type XI to form, pro-alpha2 chain (XI) is combined with two collagen chains (pro-alpha1 (XI) and pro-alpha1 (II)) to form a procollagen molecule. These procollagen molecules are processed by enzymes in the cell. Once processed, the procollagen molecules out of the cell and arranged in long thin fibrils which are bonded together in the spaces around the cells. The crosslinks result in the formation of collagen fibers XI very strong mature type. XI collagen type also helps maintain separation and diameter of the fibrils of type II collagen. The type II collagen is an important component of the eye and mature cartilage tissue. The size and arrangement of collagen fibrils type II are essential for the normal structure of these tissues.
They have identified at least 14 COL11A2 gene mutations associated with otospondilomegaepifisalia dysplasia (OSMED). Most of these mutations result in the absence of chain pro-alpha2 (XI) functional, which impairs the function of type XI collagen. Some mutations alter the coding pro-alpha2 (XI) chain and the formation of type XI collagen. XI collagen type is an important component of cartilage and other connective tissues, and causes loss or deterioration characteristic signs and symptoms of OSMED.
This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with dysplasia otospondilomegaepifisalia (OSMED), by complete PCR amplification of the exons of COL11A2 gene, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).