Osteochondritis dissecans family (osteochondritis dissecans Familial) - Gen ACAN.
Family osteochondritis dissecans is a disease that affects the joints and is associated with abnormal cartilage. A characteristic feature of family osteochondritis dissecans are areas of bone injury due to detachment of the cartilage and underlying bone from the bone end in a joint. As a result, affected individuals develop multiple lesions involving several joints, especially knees, elbows, hips and ankles. These lesions cause stiffness, pain and swelling in the joint. Other characteristic features of osteochondritis dissecans family include short stature and the development of osteoarthritis at an early age. Osteoarthritis is characterized by the breakdown of joint cartilage and underlying bone, which results in pain and stiffness and restricts the movement of the joints.
A similar disease called osteochondritis dissecans sporadic associated with a single lesion in a joint, most often knee. These cases may result from injury or repetitive use of a joint. Some people with sporadic osteochondritis dissecans develop osteoarthritis in the affected joint, especially if the injury occurs later in life after the bone has stopped growing.
This process is due to mutations in the ACAN gene, located on the long arm of chromosome 15 (15q26.1). This gene encodes a called proteoglycan aggrecan. This protein binds to other components of cartilage in a specific region of the aggrecan protein domain called the C-type lectin (CLD). Because linked sugars, aggrecan attracts water molecules and gives cartilage its gel - like structure. This feature allows the cartilage resist compression and protection of bones and joints. Although its exact function is unclear, aggrecan affects bone development.
It has identified at least one mutation in the ACAN gene in people with familial osteochondritis dissecans. This mutation changes one amino acid in the aggrecan protein. Specifically, the amino acid valine is replaced by the amino acid methionine at position 2303 of the protein (or V2303M Val2303Met), which results in an abnormal protein that is unable to bind to other components of cartilage. As a result, the cartilage is disrupted and weakened. Although it is unclear how the abnormal cartilage is involved in the development of lesions and osteoarthritis characteristic of the disease, it is likely that a disorganized network of cartilage in growing bones affect their growth, leading to short stature.
This disease is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to express the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with familial osteochondritis dissecans, by complete PCR amplification of the exons of the gene ACAN 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).