title: De novo PMP2 mutations in families with type 1 Charcot-Marie-Tooth disease.
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.
authors.affiliation: Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA Department of Medicine, Pennsylvania Hospital, University of Pennsylvania, Philadelphia, Pennsylvania 19107, USA.
authors.forename: William W
authors.initials: WW
authors.lastname: Motley
authors.affiliation: Molecular Neurogenomics Group, VIB Department of Molecular Genetics, University of Antwerp, Universiteitsplein 1, 2650-Antwerpen, Belgium Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Universiteitsplein 1, 2650-Antwerpen, Belgium.
authors.forename: Paulius
authors.initials: P
authors.lastname: Palaima
authors.affiliation: Department of Pediatrics, Division of Neurology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Sabrina W
authors.initials: SW
authors.lastname: Yum
authors.affiliation: Department of Human Genetics and Hussman Institute for Human Genomics, University of Miami, Miami, Florida 33136, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Gonzalez
authors.affiliation: Department of Human Genetics and Hussman Institute for Human Genomics, University of Miami, Miami, Florida 33136, USA.
authors.forename: Feifei
authors.initials: F
authors.lastname: Tao
authors.affiliation: Department of Neurology, Medical University of Innsbruck, Austria.
authors.forename: Julia V
authors.initials: JV
authors.lastname: Wanschitz
authors.affiliation: Department of Human Genetics and Hussman Institute for Human Genomics, University of Miami, Miami, Florida 33136, USA.
authors.forename: Alleene V
authors.initials: AV
authors.lastname: Strickland
authors.affiliation: Department of Neurology, Medical University of Innsbruck, Austria.
authors.forename: Wolfgang N
authors.initials: WN
authors.lastname: Löscher
authors.affiliation: Molecular Neurogenomics Group, VIB Department of Molecular Genetics, University of Antwerp, Universiteitsplein 1, 2650-Antwerpen, Belgium Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Universiteitsplein 1, 2650-Antwerpen, Belgium.
authors.forename: Els
authors.initials: E
authors.lastname: De Vriendt
authors.affiliation: Department of Neurology, State Hospital of Rankweil, Rankweil, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Koppi
authors.affiliation: Individualized Medical Genetics Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Livija
authors.initials: L
authors.lastname: Medne
authors.affiliation: Division of Human Genetics, Department of Pediatrics, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Andreas R
authors.initials: AR
authors.lastname: Janecke
authors.affiliation: Molecular Neurogenomics Group, VIB Department of Molecular Genetics, University of Antwerp, Universiteitsplein 1, 2650-Antwerpen, Belgium Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Universiteitsplein 1, 2650-Antwerpen, Belgium.
authors.forename: Albena
authors.initials: A
authors.lastname: Jordanova
authors.affiliation: Department of Human Genetics and Hussman Institute for Human Genomics, University of Miami, Miami, Florida 33136, USA.
authors.forename: Stephan
authors.initials: S
authors.lastname: Zuchner
authors.affiliation: Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA sscherer@mail.med.upenn.edu.
authors.forename: Steven S
authors.initials: SS
authors.lastname: Scherer
mesh_terms: D000293:Adolescent; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D059472:Exome / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018996:Myelin P2 Protein / Q000235:genetics*; D009431:Neural Conduction / Q000235:genetics; D010375:Pedigree; D055815:Young Adult
chemical_list: D018996:Myelin P2 Protein; C560555:PMP2 protein, human
keywords: CMT; Charcot-Marie-Tooth disease; PMP2; myelin P2 protein; peripheral neuropathy