Type IX collagen gene mutations can result in multiple epiphyseal dysplasia that is associated with osteochondritis dissecans and a mild myopathy - PubMed (original) (raw)

Case Reports

. 2010 Apr;152A(4):863-9.

doi: 10.1002/ajmg.a.33240.

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Case Reports

Type IX collagen gene mutations can result in multiple epiphyseal dysplasia that is associated with osteochondritis dissecans and a mild myopathy

Gail C Jackson et al. Am J Med Genet A. 2010 Apr.

Free PMC article

Abstract

Multiple epiphyseal dysplasia (MED) is a clinically variable and genetically heterogeneous disease that is characterized by mild short stature and early onset osteoarthritis. Autosomal dominant forms are caused by mutations in the genes that encode type IX collagen, cartilage oligomeric matrix protein, and matrilin-3: COL9A1, COL9A2, COL9A3, COMP, and MATN3, respectively. Splicing mutations have been identified in all three genes encoding type IX collagen and are restricted to specific exons encoding an equivalent region of the COL3 domain in all three alpha(IX) chains. MED has been associated with mild myopathy in some families, in particular one family with a COL9A3 mutation and two families with C-terminal COMP mutations. In this study we have identified COL9A2 mutations in two families with MED that also have osteochondritis dissecans and mild myopathy. This study therefore extends the range of gene-mutations that can cause MED-related myopathy. (c) 2010 Wiley-Liss, Inc.

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Figures

Fig 1

Fig 1

Pedigrees of two the families with MED presented in this study. An arrow indicates those individuals in which a COL9A2 mutation was identified. In Family 2 those individuals with semi-filled symbols were reported as affected by II-1, but this has not been independently confirmed by clinical or radiographic examination.

Fig 2

Fig 2

Radiographs of the proband (individual III-4, panels A–D) in Family 1 at 33 years of age and her eldest son (individual IV-6, panels E,F) at 3 years of age. The mother's radiographs showed (A) normal hand, (B) knees with bilateral genu varus, irregular joint surfaces, and decreased joint space, especially of the right knee, (C) lateral spine with irregular endplates of the vertebral bodies in the thoracolumbal region and (D) relatively normal hips. Radiographs of her 3-year-old son showing (E) hips and (F) the left knee. The radiographs were consistent with a diagnosis of mild MED, characterized by delayed ossification of the epiphyses. The hips were relatively spared but had small proximal femoral epiphyses, while the knees had small femoral and tibial epiphyses.

Fig 3

Fig 3

Radiographs of the proband in Family 2 (individual III-1) at age 9 years and 10 months of age showing (A) hand, (B) knee, (C) spine, and (D) hips. The radiographs were consistent with a diagnosis of MED, characterized by delayed and abnormal endochondral ossification. The hand showed marked carpal ossification delay with irregular carpal bones with a coarse internal structure. The distal epiphysis of the radius was also irregular and small. The knees had small and irregular femoral and tibial epiphyses and irregular metaphyses. The pelvis showed some flattening of the proximal femoral epiphyses but they were relatively spared. There was some irregularity of the vertebral end plates (arrow).

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