Founder SH3TC2 mutations are responsible for a CMT4C French-Canadians cluster

Neuromuscul Disord. 2008 Jun;18(6):483-92. doi: 10.1016/j.nmd.2008.04.001. Epub 2008 Jun 3.

Abstract

Charcot-Marie-Tooth polyneuropathies (CMT) are clinically and genetically heterogeneous. We describe a French-Canadian cluster of 17 recessive CMT cases belonging to 10 families with variable early-onset CMT and scoliosis. The patients demonstrate great intra- and inter-familial variability. Linkage analysis confirmed that all families are linked to CMT4C locus on chromosome 5q32 (multipoint LOD score of 9.06). Haplotype analysis suggests that two SH3TC2 mutations are present in this cohort. The majority of carrier chromosomes, 26 of 34 (76%), carry the c.2860C-->T mutation. Despite extensive sequencing, the other mutation is not yet uncovered. This study demonstrates that the clinical variability observed in CMT4C is due to other factors than the nature of the mutation and that further work is needed to better define the SH3TC2 gene to ensure the identification of all CMT4C mutations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Canada / epidemiology
  • Canada / ethnology
  • Charcot-Marie-Tooth Disease / epidemiology
  • Charcot-Marie-Tooth Disease / genetics*
  • Charcot-Marie-Tooth Disease / pathology
  • Child
  • Chromosomes, Human, Pair 5
  • Cluster Analysis
  • Family Health
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Proteins / genetics*
  • White People

Substances

  • Intracellular Signaling Peptides and Proteins
  • Proteins
  • SH3TC2 protein, human