Re-analysis of an original CMTX3 family using exome sequencing identifies a known BSCL2 mutation

Muscle Nerve. 2013 Jun;47(6):922-4. doi: 10.1002/mus.23743. Epub 2013 Mar 29.

Abstract

Introduction: Charcot-Marie-Tooth (CMT) disease is a group of peripheral neuropathies affecting both motor and sensory nerves. CMTX3 is an X-linked CMT locus, which maps to chromosome Xq26.3-q27.3. Initially, CMTX3 was mapped to a 31.2-Mb region in 2 American families. We have reexamined 1 of the original families (US-PED2) by next generation sequencing.

Methods: Three members of the family underwent exome sequencing. Candidate variants were validated by PCR and Sanger sequencing analysis.

Conclusion: No pathogenic coding variants localizing to the CMTX3 region were identified. However, exome sequencing identified a known BSCL2 mutation (N88S). This study demonstrates the power of exome sequencing as a tool to identify gene mutations for a small family in the absence of statistically significant linkage data.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Charcot-Marie-Tooth Disease / genetics*
  • Exome / genetics
  • Female
  • GTP-Binding Protein gamma Subunits / genetics*
  • Humans
  • Male
  • Mutation, Missense
  • Pedigree
  • Polymorphism, Single Nucleotide
  • Sequence Analysis, DNA

Substances

  • BSCL2 protein, human
  • GTP-Binding Protein gamma Subunits

Supplementary concepts

  • Charcot-Marie-Tooth disease, X-linked recessive, 3