Multiple osteophyte dysplasia (MED) is a rare hereditary osteochondral dysplasia. It is a systemic osteophyte dysplasia caused by defects in structural proteins and cell membrane transport proteins in the extracellular matrix of the cartilage, mainly affecting the ends of the arm and leg bones. Both clinical and clinical manifestations are heterogeneous. The genetic pattern is a completely autosomal dominant inheritance, and a few cases are recessive. The changes in the epiphysis are usually symmetrical, and there may be only a few of the affected epiphyses or changes in the major joints. The most common sites are the hips, shoulders and knees. Currently, there are three types of clinical classification described. The first type is Ribbing type, that is, light type, characterized by short stature, flat epiphysis, early-onset osteoarthritis of the hip, and mild or no involvement of the wrist. The other type is Fairbank type, that is, heavy type, which is characterized by dwarfism, short and thick fingers, and small epiphysis of multiple joints, especially small and round hip and femoral head. Different from other types of MED flat femoral head, the metacarpal and phalangeal epiphyses are irregular, and severe changes of carpal and tarsal bones are also observed.
Some types of autosomal dominant MED are caused by COMP gene mutations, while others are caused by the mutations of the COL9A1 gene encoding collagen alpha 1 strand, COL9A2 gene encoding alpha 2 strand, COL9A3 gene encoding alpha 3 strand and MATN3 gene, respectively. The COMP gene is located on chromosome 19. The cartilage oligomer matrix protein encoded by this gene is a homologous pentameric glycoprotein, mostly presents in the extracellular matrix (ECM) of cartilage, tendon and ligament. MED growth plate chondrocytes have a large, lamellar and rough endoplasmic reticulum containing a large number of potential proteins including COMP, collagen type IX and matrillin-3. It has been reported that COMP mutations lead to protein misfolding, most of which bind to chaperones and thus do not degrade in the rough endoplasmic reticulum. The large accumulation of such intracellular proteins is likely to destroy the normal function of chondrocytes, leading to cell death. Type IX collagen is composed of alpha 1 alpha 2 alpha 3 strands encoded by COL9A1, COL9A2 and COL9A3 gene, respectively. Type IX collagen’s functions are to maintain articular cartilage integrity and to participate in the stability of the cartilage matrix environment. It may interact directly or indirectly with chondrocyte membrane receptors, providing information to cells based on changes in their physical and chemical properties. Type IX collagen binds to COMP with a high degree of affinity, and the interaction between the two may be the mechanism of type IX collagen mutations, and can also cause MED. MATN3 mutations disrupt the secretion of abnormal matrilin-3 by causing misfolding of the A-domain, which results in intracellular retention of the mutant protein and causes MED. In addition, mutations in the gene encoding the sulfate transporter 26A2 (SLC26A2) can result in the production of autosomal recessive MED.
CD-Genomics provides a custom multiple epiphyseal dysplasia panel containing optimized genes that are reported associated with the increase of risk of multiple epiphyseal dysplasia. You can select the genes only you require to customize your exclusive panel. Targeted DNA sequencing by Illumina MiSeq system/Ion PGM system is provided to help study the related mechanisms of the regulation of regeneration and repair after normal skeletal development and bone injury, and also contribute to the research of precise treatment of this disease.
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