A Japanese familial case of Schmid metaphyseal chondrodysplasia with a novel mutation in <i>COL10A1</i>

Abstract

Schmid metaphyseal chondrodysplasia (SMCD; OMIM #156500) is an autosomal dominant skeletal dysplasia, characterized by short stature with short legs, bowing of the long bones, and waddling gait. Radiographic features include metaphyseal irregularities with fraying and splaying, and coxa vara, which is defined as a deformity of the hip, wherein the angle between the head and the shaft of the femur is reduced to less than 120 degrees (1). SMCD is caused by heterozygous mutations in COL10A1 (MIM #120110), encoding the α1(X) chains of type X collagen, which is a homotrimeric molecule that consists of three identical α1(X) chains. Each α1(X) chain contains a core triple helical domain, composed of uninterrupted repeats of the Gly-Xaa-Yaa tripeptide, flanked by two globular domains (NC2 and NC1) at both the amino and carboxyl-terminal ends (2). To date, 48 COL10A1 mutations have been reported in families with SMCD of different ethnic origin (Human Gene Mutation Database; http://www.hgmd.cf.ac.uk/ac). Most COL10A1 mutations identified to date were located in the NC1 domain, which contains motifs that promote trimerization of α1(X) chains and subsequent formation of the triple helix to yield stable collagen X molecules. Here, we report a Japanese familial case of SMCD with a novel mutation in COL10A1.