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

Hum Mutat. 2015 Oct;36(10):1004-8. doi: 10.1002/humu.22839. Epub 2015 Aug 6.


Progressive pseudorheumatoid dysplasia (PPRD) is a rare, autosomal-recessive condition characterized by mild spondyloepiphyseal dysplasia (SED) and severe, progressive, early-onset arthritis due to WISP3 mutations. 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.

Keywords: PPRD; SED; Stanescu; skeletal dysplasia; spondyloepiphyseal dysplasia tarda with progressive arthropathy; type II collagenopathy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Collagen Type II / genetics*
  • Exome
  • Female
  • Humans
  • Joint Diseases / congenital*
  • Joint Diseases / diagnostic imaging
  • Joint Diseases / genetics
  • Male
  • Osteochondrodysplasias / diagnostic imaging
  • Osteochondrodysplasias / genetics*
  • Pedigree
  • Polymorphism, Single Nucleotide*
  • Radiography
  • Sequence Analysis, DNA / methods


  • COL2A1 protein, human
  • Collagen Type II

Supplementary concepts

  • Arthropathy, progressive pseudorheumatoid, of childhood