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

William W. Motley, Paulius Palaima, Sabrina W. Yum, Michael A. Gonzalez, Feifei Tao, Julia V. Wanschitz, Alleene V. Strickland, Wolfgang N. Löscher, Els De Vriendt, Stefan Koppi, Livija Medne, Andreas R. Janecke, Albena Jordanova, Stephan L Zuchner, Steven S. Scherer

Research output: Contribution to journalArticle

18 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1649-1656
Number of pages8
JournalBrain
Volume139
Issue number6
DOIs
StatePublished - 2016

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Keywords

  • Charcot-Marie-Tooth disease
  • CMT, myelin P2 protein
  • Peripheral neuropathy
  • PMP2

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Motley, W. W., Palaima, P., Yum, S. W., Gonzalez, M. A., Tao, F., Wanschitz, J. V., Strickland, A. V., Löscher, W. N., De Vriendt, E., Koppi, S., Medne, L., Janecke, A. R., Jordanova, A., Zuchner, S. L., & Scherer, S. S. (2016). De novo PMP2 mutations in families with type 1 Charcot-Marie-Tooth disease. Brain, 139(6), 1649-1656. https://doi.org/10.1093/brain/aww055