Mutations in a gene encoding a novel SH3/TPR domain protein cause autosomal recessive Charcot-Marie-Tooth type 4C neuropathy
Détails
ID Serval
serval:BIB_664180AFE4FC
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Mutations in a gene encoding a novel SH3/TPR domain protein cause autosomal recessive Charcot-Marie-Tooth type 4C neuropathy
Périodique
American Journal of Human Genetics
ISSN
0002-9297 (Print)
Statut éditorial
Publié
Date de publication
11/2003
Volume
73
Numéro
5
Pages
1106-19
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Nov
Research Support, Non-U.S. Gov't --- Old month value: Nov
Résumé
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.
Mots-clé
Adolescent
Adult
Alternative Splicing/genetics
Amino Acid Sequence
Animals
Base Sequence
Charcot-Marie-Tooth Disease/*genetics/physiopathology
Child
Child, Preschool
Chromosomes, Human, Pair 5/genetics
Consanguinity
Female
Gene Expression Profiling
Genes, Recessive/*genetics
Genome, Human
Haplotypes/genetics
Humans
Infant
Male
Middle Aged
Molecular Sequence Data
Mutation/*genetics
Pedigree
Phenotype
Proteins/*chemistry/*genetics
RNA, Messenger/analysis/genetics
*src Homology Domains
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 15:12
Dernière modification de la notice
20/08/2019 15:22