Mutations in a Gene Encoding a Novel SH3/TPR Domain Protein Cause Autosomal Recessive Charcot-Marie-Tooth Type 4C Neuropathy

Jan Senderek; Carsten Bergmann; Claudia Stendel; Jutta Kirfel; Nathalie Verpoorten; Peter De Jonghe; Vincent Timmerman; Roman Chrast; Mark H.G Verheijen; Greg Lemke; Esra Battaloglu; Yesim Parman; Sevim Erdem; Ersin Tan; Haluk Topaloglu; Andreas Hahn; Wolfgang Müller-Felber; Nicolò Rizzuto; Gian Maria Fabrizi; Manfred Stuhrmann; Sabine Rudnik-Schöneborn; Stephan Züchner; J Michael Schröder; Eckhard Buchheim; Volker Straub; Jörg Klepper; Kathrin Huehne; Bernd Rautenstrauss; Reinhard Büttner; Eva Nelis; Klaus Zerres

doi:10.1086/379525

Back

Mutations in a Gene Encoding a Novel SH3/TPR Domain Protein Cause Autosomal Recessive Charcot-Marie-Tooth Type 4C Neuropathy

Journal article

Open access

Peer reviewed

Mutations in a Gene Encoding a Novel SH3/TPR Domain Protein Cause Autosomal Recessive Charcot-Marie-Tooth Type 4C Neuropathy

Jan Senderek, Carsten Bergmann, Claudia Stendel, Jutta Kirfel, Nathalie Verpoorten, Peter De Jonghe, Vincent Timmerman, Roman Chrast, Mark H.G Verheijen, Greg Lemke, …

American journal of human genetics, Vol.73(5), pp.1106-1119

2003

DOI: https://doi.org/10.1086/379525

PMCID: PMC1180490

PMID: 14574644

Abstract

Charcot-Marie-Tooth disease type 4C (CMT4C) is a childhood-onset demyelinating form of hereditary motor and sensory neuropathy associated with an early-onset scoliosis and a distinct Schwann cell pathology. CMT4C is inherited as an autosomal recessive trait and has been mapped to a 13-cM linkage interval on chromosome 5q23-q33. By homozygosity mapping and allele-sharing analysis, we refined the CMT4C locus to a suggestive critical region of 1.7 Mb. We subsequently identified mutations in an uncharacterized transcript, KIAA1985, in 12 families with autosomal recessive neuropathy. We observed eight distinct protein-truncating mutations and three nonconservative missense mutations affecting amino acids conserved through evolution. In all families, we identified a mutation on each disease allele, either in the homozygous or in the compound heterozygous state. The CMT4C gene is strongly expressed in neural tissues, including peripheral nerve tissue. The translated protein defines a new protein family of unknown function with putative orthologues in vertebrates. Comparative sequence alignments indicate that members of this protein family contain multiple SH3 and TPR domains that are likely involved in the formation of protein complexes.

Files and links (1)

url

https://doi.org/10.1086/379525View

Published (Version of record) Open

Metrics

14 Record Views

149 Times Cited - Web of Science

See more details

InCites Highlights

These are selected metrics from InCites Benchmarking & Analytics tool, related to this output

Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.253 Nerve Disorders; 1.253.1972 Charcot-Marie-Tooth Disease
Web Of Science research areas: Genetics & Heredity
ESI research areas: Molecular Biology & Genetics

UN Sustainable Development Goals (SDGs)

This output has contributed to the advancement of the following goals:

Source: InCites

Details

Title: Mutations in a Gene Encoding a Novel SH3/TPR Domain Protein Cause Autosomal Recessive Charcot-Marie-Tooth Type 4C Neuropathy
Creators: Jan Senderek - Department of Human Genetics, Aachen University of Technology, Aachen, Germany
Carsten Bergmann - Department of Human Genetics, Aachen University of Technology, Aachen, Germany
Claudia Stendel - Department of Human Genetics, Aachen University of Technology, Aachen, Germany
Jutta Kirfel - Institute of Pathology, University of Bonn, Bonn
Nathalie Verpoorten - Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerp
Peter De Jonghe - Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerp
Vincent Timmerman - Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerp
Roman Chrast - Molecular Neurobiology Laboratory, The Salk Institute, La Jolla, CA
Mark H.G Verheijen - Molecular Neurobiology Laboratory, The Salk Institute, La Jolla, CA
Greg Lemke - Molecular Neurobiology Laboratory, The Salk Institute, La Jolla, CA
Esra Battaloglu - Department of Molecular Biology and Genetics, Bogaziçi University, Istanbul
Yesim Parman - Neurology Department, Istanbul Faculty of Medicine, Istanbul
Sevim Erdem - Department of Neurology and Neuromuscular Diseases Research Laboratory, Hacettepe University, Ankara, Turkey
Ersin Tan - Department of Neurology and Neuromuscular Diseases Research Laboratory, Hacettepe University, Ankara, Turkey
Haluk Topaloglu - Department of Pediatric Neurology, Hacettepe Children’s Hospital, Ankara, Turkey
Andreas Hahn - Department of Neuropediatrics, Justus-Liebig-University, Giessen, Germany
Wolfgang Müller-Felber - Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilian-University, Munich
Nicolò Rizzuto - Department of Neurological and Visual Sciences, Section of Neurology, University of Verona, Verona
Gian Maria Fabrizi - Department of Neurological and Visual Sciences, Section of Neurology, University of Verona, Verona
Manfred Stuhrmann - Institute of Human Genetics, Medical School Hannover, Hannover
Sabine Rudnik-Schöneborn - Department of Human Genetics, Aachen University of Technology, Aachen, Germany
Stephan Züchner - Department of Neuropathology, Aachen University of Technology, Aachen, Germany
J Michael Schröder - Department of Neuropathology, Aachen University of Technology, Aachen, Germany
Eckhard Buchheim - Department of Paediatrics, Esslingen Community Hospital, Esslingen, Germany
Volker Straub - Department of Pediatrics and Pediatric Neurology, University Hospital Essen, Essen, Germany
Jörg Klepper - Department of Pediatrics and Pediatric Neurology, University Hospital Essen, Essen, Germany
Kathrin Huehne - Department of Human Genetics, Friedrich-Alexander University, Erlangen-Nuremberg, Germany
Bernd Rautenstrauss - Department of Human Genetics, Friedrich-Alexander University, Erlangen-Nuremberg, Germany
Reinhard Büttner - Institute of Pathology, University of Bonn, Bonn
Eva Nelis - Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerp
Klaus Zerres - Department of Human Genetics, Aachen University of Technology, Aachen, Germany
Publication Details: American journal of human genetics, Vol.73(5), pp.1106-1119
Publisher: Elsevier Inc
Academic Unit: Leadership Department; Miller School of Medicine; John P. Hussman Institute for Human Genomics
Language: English
Resource Type: Journal article
PMID: 14574644
PMCID: PMC1180490
Record Identifier: 991031560435902976