A Missense Mutation in COL10A1 Gene in a Pakistani Consanguineous Family with Schmid Type Metaphyseal Chondrodysplasia

Schmid-type metaphyseal chondrodysplasia (MCDS) is an autosomal dominant disorder caused by COL10A1 mutations and is characterized by short stature, waddling gait, coxa vara and bowing of the long bones. A large family from Southern Punjab in Pakistan suffering from MCDS following autosomal dominant mode of inheritance were enrolled in present study. Whole exome sequencing (WES) approach was adopted to identify causative agent of dwarfism that reveled a previously reported a missense mutation (c.2011A > G, p.Ser 671Pro) in exon 3 of COL10A1 gene. Sanger sequencing confirmed these mutations in all enrolled subjects and mutation followed Mendalian pattern of inheritance. Multiple sequence alignment by Clustal Omega revealed that domain of COL10A1 containing mutations is highly conserved. In conclusion, we are reporting a previously reported a missense mutation in COL10A1 gene that is causing MCDS in a large consanguineous Pakistani family.