Six New Gap Junction Beta 1 Gene Mutations and Their Phenotypic Expression in Czech Patients with Charcot-Marie-Tooth Disease
- 1 February 2010
- journal article
- Published by Mary Ann Liebert Inc in Genetic Testing and Molecular Biomarkers
- Vol. 14 (1), 3-7
- https://doi.org/10.1089/gtmb.2009.0093
Abstract
X-linked Charcot-Marie-Tooth (CMTX) disease is a hereditary motor and sensory neuropathy caused by mutations in the gap junction beta 1 gene (GJB1 codes for connexin 32). In this study we report six novel mutations p.Met1Arg, p.Leu9Phe, p.Ser17Tyr, p.Val63Phe, p.Val170Ile, and p.Leu212Phe in GJB1 and their phenotypic expression. These mutations affect both intracellular and extracellular parts of the GJB1 protein. The screened patients had previously excluded the duplication/deletion on 17p11.2 and the male-to-male transfer in the pedigree. Except p.Val170Ile, all reported mutations segregated with the CMT phenotype in the families and caused CMTX1 neuropathy. Mutations were not found in 200 control DNA samples. Additionally, we performed in silico analysis of the novel mutations with the program PANTHER. The PANTHER scored five mutations, all but p.Val170Ile, as likely deleterious and supported the pathogenicity of the found mutations. These results provided evidence that these five mutations are causative for CMTX1.Keywords
This publication has 20 references indexed in Scilit:
- Clinical and molecular analysis of X‐linked Charcot‐Marie‐Tooth disease type 1 in Spanish populationClinical Genetics, 2006
- A new de novo mutation of the connexin-32 gene in a patient with X-linked Charcot-Marie-Tooth type 1 disease.Neurological Sciences, 2000
- Genotype/Phenotype Correlations in X‐Linked Dominant Charcot‐Marie‐Tooth DiseaseAnnals of the New York Academy of Sciences, 1999
- Genotype/phenotype correlation in affected individuals of a family with a deletion of the entire coding sequence of the connexin 32 geneHuman Genetics, 1998
- Connexin32 and X-linked Charcot–Marie–Tooth DiseaseNeurobiology of Disease, 1997
- Charcot–marie–tooth neuropathies: From clinical description to molecular geneticsMuscle & Nerve, 1995
- Mutations in the connexin 32 gene in X-linked dominant Charcot- Marie - Tooth disease (CMTX1)Human Molecular Genetics, 1994
- Connexin Mutations in X-Linked Charcot-Marie-Tooth DiseaseScience, 1993
- X-LINKED DOMINANT HEREDITARY MOTOR AND SENSORY NEUROPATHYBrain, 1990
- THE CLINICAL FEATURES OF HEREDITARY MOTOR AND SENSORY NEUROPATHY TYPES I AND IIBrain, 1980