A novel SOX9 H169Q mutation in a family with overlapping phenotype of mild campomelic dysplasia and small patella syndrome

Am J Med Genet A. 2013 Oct;161A(10):2528-34. doi: 10.1002/ajmg.a.36134. Epub 2013 Aug 16.

Abstract

The phenotypic similarities have been demonstrated between non-lethal campomelic dysplasia (CD) and small patella syndrome (SPS), in which different genetic defects have been identified. We report on a familial case of skeletal dysplasia with overlapping phenotype of mild CD and SPS, including defective ischio-pubic ossification, elongated femoral neck, hypoplastic patellae, and increased space between the first and the second toes (sandal gap). Direct sequencing analysis demonstrated a novel missense mutation (p.H169Q) within the coding region of the SOX9 gene and negative for TBX4 mutations. Functional analysis of the p.H169Q mutant revealed reduced but not fully abolished transactivation capacity of the mutated protein. Retained residual SOX9 function might contribute to an extremely mild CD phenotype in the present cases. © 2013 Wiley Periodicals, Inc.

Keywords: SOX9; campomelic dysplasia; familial; small patella syndrome.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bone Diseases, Developmental / diagnosis
  • Bone Diseases, Developmental / genetics*
  • COS Cells
  • Campomelic Dysplasia / diagnosis
  • Campomelic Dysplasia / genetics*
  • Child
  • Chlorocebus aethiops
  • Computational Biology
  • Conserved Sequence
  • Genetic Variation
  • Hip / abnormalities*
  • Humans
  • Ischium / abnormalities*
  • Male
  • Molecular Sequence Data
  • Mutation*
  • Patella / abnormalities*
  • Phenotype*
  • Pierre Robin Syndrome / diagnosis
  • Pierre Robin Syndrome / genetics*
  • SOX9 Transcription Factor / genetics*
  • SOX9 Transcription Factor / metabolism
  • Sequence Alignment
  • Syndrome
  • T-Box Domain Proteins / genetics

Substances

  • SOX9 Transcription Factor
  • SOX9 protein, human
  • T-Box Domain Proteins
  • TBX4 protein, human

Supplementary concepts

  • Ischiopatellar dysplasia
  • Pierre Robin sequence with pectus excavatum and rib and scapular anomalies