De novo PMP2 mutations in families with type 1 Charcot-Marie-Tooth disease

Brain. 2016 Jun;139(Pt 6):1649-56. doi: 10.1093/brain/aww055. Epub 2016 Mar 23.

Abstract

We performed whole exome sequencing on a patient with Charcot-Marie-Tooth disease type 1 and identified a de novo mutation in PMP2, the gene that encodes the myelin P2 protein. This mutation (p.Ile52Thr) was passed from the proband to his one affected son, and segregates with clinical and electrophysiological evidence of demyelinating neuropathy. We then screened a cohort of 136 European probands with uncharacterized genetic cause of Charcot-Marie-Tooth disease and identified another family with Charcot-Marie-Tooth disease type 1 that has a mutation affecting an adjacent amino acid (p.Thr51Pro), which segregates with disease. Our genetic and clinical findings in these kindred demonstrate that dominant PMP2 mutations cause Charcot-Marie-Tooth disease type 1.

Keywords: CMT; Charcot-Marie-Tooth disease; PMP2; myelin P2 protein; peripheral neuropathy.

Publication types

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

MeSH terms

  • Adolescent
  • Charcot-Marie-Tooth Disease / genetics*
  • Exome / genetics
  • Female
  • Genetic Predisposition to Disease / genetics
  • Haplotypes
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Myelin P2 Protein / genetics*
  • Neural Conduction / genetics
  • Pedigree
  • Young Adult

Substances

  • Myelin P2 Protein
  • PMP2 protein, human