This mutation has also been designated arg275-to-cys (R275C) based on a different numbering system.
In a family living in the Chiloe Islands, Chile, Williams et al. (1993) demonstrated a heterozygous arg75-to-cys (R75C) mutation in the COL2A1 gene as the basis of spondyloepiphyseal dysplasia with shortened metacarpals and metatarsals, precocious osteoarthritis, and periarticular apatite-like calcific deposits. Seven individuals were involved in 3 generations of the family. Complete physical examination, anthropometric measurements, and radiographic studies of the spine and peripheral joints in 16 family members revealed that 7 had spondyloepiphyseal dysplasia tarda, brachydactyly, precocious osteoarthritis, and periarticular calcification, while 2 others had the same syndrome without brachydactyly (Reginato et al., 1994). The relationship of this type of SEDT to familial calcium pyrophosphate dihydrate deposition disease (118600) and idiopathic hip dysplasia, both endemic in Chiloe Islanders, required further investigation.
Hoornaert et al. (2007) performed targeted sequencing of exon 13 of the COL2A1 gene in patients with Czech dysplasia (609162) because of phenotypic similarities between individuals with this dysplasia and patients with the R75C mutation. They identified heterozygosity for the R75C mutation in 5 patients with Czech dysplasia, including 2 of the 4 original patients described with this disorder. All affected individuals had normal height, spondyloarthropathy, and short postaxial toes.
In an affected father, daughter, and son from a Japanese family with Czech dysplasia, Matsui et al. (2009) identified heterozygosity for the R275C mutation in the COL2A1 gene. The mutation was not found in the unaffected mother. The authors stated that this was the first reported family with Czech dysplasia that was not of European ancestry, and family history was consistent with de novo occurrence of the disease in the father.
