A novel COL10A1 mutation in a Chinese pedigree with Schmid type metaphyseal chondrodysplasia

Schmid type metaphyseal chondrodysplasia (MCDS) is a kind of autosomal inherited epiphyseal dysplasia caused by a mutation of the COL10A1 gene. Clinical expression of this mutation includes a waddling gait, coxa vara, genu varus or genu valgus and shortened lower limbs among others. To date, over 40 kinds of heterozygous mutations have been identified in the collagen domain of COL10A1 but data on family pedigrees for these is lacking.

Nineteen people without a history of interbreeding were selected for the three generations pedigree of MCDS. The proband is a 13 year-old boy with short limbs, hip varus, and tibial varus. In this group, seven people had MCDS (two men, five women). Blood samples for DNA extraction and mutational analysis were collected to sequence the CLO10A1 gene.

Chromas atlas analysis and monoclonal sequencing revealed that 7 of the patients in the family are missing a C nucleotide in the third exon of the COL10A1 gene (c.2005delC).

The COL10A1 gene mutation results in a frameshift mutation from codon 669, the substitution of 7 amino acids, and premature termination of expression (p.his669thrfsX8). In contrast to the other mutations identified, c.2005delC is close to the C-terminus of the protein sequence and may result in genetic heterogeneity of the Chinese population.