Charcot-Marie-Tooth-Neuropathie Typ 2 : neue Myelinprotein-P0-Punktmutationen und Haplotypenanalyse in europäischen Familien
type: CreativeWork
description: The dominant forms of hereditary motor and sensory neuropathies of Charcot Marie Tooth type (CMT) are among the most common inherited diseases in humans. With respect to electroneurography and nerve pathology, CMT is subdivided in demyelinating CMT1 and axonal CMT2. Causative gene mutations can be identified in about 80-90% of CMT1 patients while no major CMT2 gene has been identified so far. In the present study, 49 CMT2 patients were tested for mutations in the myelin protein zero (P0, MPZ) gene that had initially been thought to be exclusively involved in the advent of demyelinating hereditary neuropathies. Three heterozygous single nucleotide changes were detected: two novel missense mutations, Asp61Gly and Tyr119Cys, and the known Thr124Met substitution, that had already been reported in several CMT patients from different European countries. Haplotype analysis for the P0 locus proved that the genealogical origin of the 124Met allele is different in the German, Italian, and French/Belgian populations. P0 mutations account for about 5% of CMT2 cases. As the frequency of connexin32 gene mutations is around 10% in CMT2, mutation analysis of both genes is expected to disclose the molecular cause in 1 out of 6 CMT2 patients. Haplotype diversity for the recurrent Thr124Met amino acid substitution suggests a mutation hotspot at the Thr124 codon. This peculiar genotype is presumed to make up a considerable proportion of P0 mutations in CMT2.
abstract: The dominant forms of hereditary motor and sensory neuropathies of Charcot Marie Tooth type (CMT) are among the most common inherited diseases in humans. With respect to electroneurography and nerve pathology, CMT is subdivided in demyelinating CMT1 and axonal CMT2. Causative gene mutations can be identified in about 80-90% of CMT1 patients while no major CMT2 gene has been identified so far. In the present study, 49 CMT2 patients were tested for mutations in the myelin protein zero (P0, MPZ) gene that had initially been thought to be exclusively involved in the advent of demyelinating hereditary neuropathies. Three heterozygous single nucleotide changes were detected: two novel missense mutations, Asp61Gly and Tyr119Cys, and the known Thr124Met substitution, that had already been reported in several CMT patients from different European countries. Haplotype analysis for the P0 locus proved that the genealogical origin of the 124Met allele is different in the German, Italian, and French/Belgian populations. P0 mutations account for about 5% of CMT2 cases. As the frequency of connexin32 gene mutations is around 10% in CMT2, mutation analysis of both genes is expected to disclose the molecular cause in 1 out of 6 CMT2 patients. Haplotype diversity for the recurrent Thr124Met amino acid substitution suggests a mutation hotspot at the Thr124 codon. This peculiar genotype is presumed to make up a considerable proportion of P0 mutations in CMT2.
author: Senderek, Jan Peter
language: ger
keywords: info:eu-repo/classification/ddc/610, Medizin, Charcot-Marie-Tooth Neuropathie, Hereditäre motorische und sensorische Neuropathie, P0-Gen, Mutation
date published: 2002
date modified: 2026-07-30T19:42:31Z
provider: RWTH Aachen University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Publikationsserver der RWTH Aachen University