Compound heterozygosity of SHOX-encompassing and downstream PAR1 deletions results in Langer mesomelic dysplasia (LMD)

Am J Med Genet A. 2007 May 1;143A(9):933-8. doi: 10.1002/ajmg.a.31676.

Abstract

We present the clinical and molecular characteristics of a multi-generation family in which the proband presented with clinical features of Langer mesomelic dysplasia (LMD) whilst different family members had a diagnosis of Léri-Weill dyschondrosteosis (LWD) and/or pseudoachondroplasia (PSACH). In the LMD proband two different deletions were identified in the pseudoautosomal 1 region (PAR1) of the X and Y chromosomes: a SHOX-encompassing deletion inherited from his father and a downstream PAR1 deletion, which did not include SHOX, inherited from his mother. The individuals with PSACH features presented the previously described G719D mutation in the C-terminal globular domain of the cartilage oligomeric matrix protein gene (COMP). The LMD proband described here represents the first LMD case due to compound heterozygosity for deletions of the two different PAR1 regions, SHOX-encompassing and downstream from SHOX, that have been shown to be implicated in the pathogenesis of LWD and LMD.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Chromosome Deletion*
  • Female
  • Homeodomain Proteins / genetics*
  • Humans
  • Loss of Heterozygosity*
  • Male
  • Middle Aged
  • Osteochondrodysplasias / genetics*
  • Pedigree
  • Receptor, PAR-1 / genetics*
  • Short Stature Homeobox Protein

Substances

  • Homeodomain Proteins
  • Receptor, PAR-1
  • SHOX protein, human
  • Short Stature Homeobox Protein

Associated data

  • OMIM/127300
  • OMIM/249700