Novel DDR2 mutation identified by whole exome sequencing in a Moroccan patient with spondylo-meta-epiphyseal dysplasia, short limb-abnormal calcification type

Am J Med Genet A. 2016 Feb;170A(2):460-465. doi: 10.1002/ajmg.a.37426. Epub 2015 Oct 13.

Abstract

Spondylo-meta-epiphyseal dysplasia (SMED), short limb-abnormal calcification type (SMED, SL-AC), is a very rare autosomal recessive disorder with various skeletal changes characterized by premature calcification leading to severe disproportionate short stature. Twenty-two patients have been reported until now, but only five mutations (four missense and one splice-site) in the conserved sequence encoding the tyrosine kinase domain of the DDR2 gene has been identified. We report here a novel DDR2 missense mutation, c.370C > T (p.Arg124Trp) in a Moroccan girl with SMED, SL-AC, identified by whole exome sequencing. Our study has expanded the mutational spectrum of this rare disease and it has shown that exome sequencing is a powerful and cost-effective tool for the diagnosis of clinically heterogeneous disorders such as SMED.

Keywords: DDR2; exome sequencing; novel mutation; short limb-abnormal calcification type; spondylo-meta-epiphyseal dysplasia.

Publication types

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

MeSH terms

  • Calcinosis / genetics*
  • Calcinosis / pathology*
  • Child, Preschool
  • Discoidin Domain Receptors
  • Dwarfism / genetics*
  • Dwarfism / pathology*
  • Exome / genetics*
  • Female
  • Genome, Human
  • High-Throughput Nucleotide Sequencing / methods
  • Humans
  • Morocco
  • Mutation, Missense / genetics*
  • Osteochondrodysplasias / genetics*
  • Osteochondrodysplasias / pathology*
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Receptors, Mitogen / genetics*

Substances

  • Receptors, Mitogen
  • Discoidin Domain Receptors
  • Receptor Protein-Tyrosine Kinases

Supplementary concepts

  • Spondylometaepiphyseal Dysplasia, Short Limb-Hand Type