Linkage and mutation analysis in an extended family with Charcot-Marie-Tooth disease type 1B.
- 1 October 1994
- journal article
- case report
- Published by BMJ in Journal of Medical Genetics
- Vol. 31 (10) , 811-815
- https://doi.org/10.1136/jmg.31.10.811
Abstract
Charcot-Marie-Tooth disease type 1 (CMT1) or hereditary motor and sensory neuropathy type I (HMSNI) is an autosomal dominant peripheral neuropathy. In most families the disease segregates with a 1.5 Mb duplication on chromosome 17p11.2 (CMT1A). A few patients have been found with point mutations in the PMP-22 gene. In some families linkage has been found with markers located on chromosome 1q21-q25 (CMT1B) and more recently mutations have been identified in the P0 gene. We analysed an extended CMT1 pedigree (CMT-B) without the CMT1A duplication. Significant positive linkage with chromosome 1 indicated that this family is of the CMT1B subtype. Sequencing of the candidate gene P0 located in chromosome band 1q21-q23 showed a C to A point mutation at position 446 in exon 3 resulting in an Asp134Glu substitution. Since the P0 mutation cosegregated with CMT1 disease we suggest that this mutation is the primary genetic cause of CMT1B in family CMT-B.Keywords
This publication has 20 references indexed in Scilit:
- Charcot-Marie-tooth disease: a new paradigm for the mechanism of inherited diseaseTrends in Genetics, 1994
- Mutation of the myelin Po gene in Charcot — Marie — Tooth neuropathy type 1BHuman Molecular Genetics, 1993
- Deletion of the serine 34 codon from the major peripheral myelin protein P0 gene in Charcot–Marie–Tooth disease type 1BNature Genetics, 1993
- Charcot–Marie–Tooth neuropathy type 1B is associated with mutations of the myelin P0 geneNature Genetics, 1993
- Construction of a physical map on mouse and human chromosome 1: comparison of 13 Mb of mouse and 11 Mb of human DNAHuman Molecular Genetics, 1992
- The peripheral myelin protein gene PMP–22 is contained within the Charcot–Marie–Tooth disease type 1A duplicationNature Genetics, 1992
- Estimation of the size of the chromosome 17p11.2 duplication in Charcot-Marie-Tooth neuropathy type 1a (CMT1a). HMSN Collaborative Research Group.Journal of Medical Genetics, 1992
- Isolation and sequence determination of cDNA encoding the major structural protein of human peripheral myelinBiochemical and Biophysical Research Communications, 1991
- Population frequencies of inherited neuromuscular diseases—A world surveyNeuromuscular Disorders, 1991
- A genetic map of human chromosome 17pGenomics, 1990