Novel COL9A3 mutation in a family with multiple epiphyseal dysplasia.

Multiple epiphyseal dysplasia (MED) is a common skeletal dysplasia characterized by mild to moderate short stature, early-onset of osteoarthritis (OA) mainly in the hip and knee joints, and abnormally small and/or irregular epiphyses. MED is clinically and genetically heterogeneous. Six causative genes of MED have been reported, including type IX collagen genes (COL9A1, COL9A2, COL9A3). All the type IX collagen mutations previously reported cause exon skipping that loses the COL3 domain. Here we have identified a novel COL9A3 mutation co-segregating in a three-generation family with MED. The mutation (IVS3 + 5G > A) was speculated to lose the COL3 domain by skipping of exon 3, which was confirmed by in vitro analysis. The patients were of normal height and had minimal complaints with phenotypes being more severe in male patients. The radiographic phenotypes of the patients were relatively milder than those of previously reported cases, and were indistinguishable to common, idiopathic OA.