RESEARCH ARTICLE Two Novel Mutations in Myosin Binding Protein C Slow Causing Distal Arthrogryposis Type 2 in Two Large Han Chinese Families May Suggest Important Functional Role of

Distal arthrogryposes (DAs) are a group of disorders that mainly involve the distal parts of the limbs and at least ten different DAs have been described to date. DAs are mostly de-scribed as autosomal dominant disorders with variable expressivity and incomplete pene-trance, but recently autosomal recessive pattern was reported in distal arthrogryposis type 5D. Mutations in the contractile genes are found in about 50 % of all DA patients. Of these genes, mutations in the gene encoding myosin binding protein C slowMYBPC1 were re-cently identified in two families with distal arthrogryposis type 1B. Here, we described two large Chinese families with autosomal dominant distal arthrogryposis type 2(DA2) with in-complete penetrance and variable expressivity. Some unique overextension contractures of the lower limbs and some distinctive facial features were present in our DA2 pedigrees. We performed follow-up DNA sequencing after linkage mapping and first identified two novelMYBPC1mutations (c.1075G>A [p.E359K] and c.956C>T [p.P319L]) responsible for these Chinese DA2 families of which one introduced by germline mosacism. Each muta-tion was found to cosegregate with the DA2 phenotype in each family but not in populatio