Novel COL2A1 variant (c.619GA p.Gly207Arg) manifesting as a phenotype similar to progressive pseudorheumatoid dysplasia and spondyloepiphyseal dysplasia Stanescu type

摘要

Progressive pseudorheumatoid dysplasia (PPRD) is a rare, autosomal recessive condition characterized by mild spondyloepiphyseal dysplasia and severe, progressive, early-onset arthritis due to WISP3 mutations. Spondyloepiphyseal dysplasia (SED), Stanescu type, is a vaguely delineated autosomal dominant dysplasia of unknown genetic etiology. Here we report three individuals from two unrelated families with radiological features similar to PPRD and SED, Stanescu type who share the same novel COL2A1 variant and were matched following discussion at an academic conference. In the first family, we performed whole exome sequencing on three family members, two of whom have a PPRD-like phenotype, and identified a heterozygous variant (c.619G>A, p.Gly207Arg) in both affected individuals. Independently, targeted sequencing of the COL2A1 gene in an unrelated proband with a similar phenotype identified the same heterozygous variant. We suggest that the p.Gly207Arg variant causes a distinct type II collagenopathy with features of PPRD and SED, Stanescu type.