1. Charcot–Marie–Tooth neuropathy type 1B is associated with mutations of the myelin P0 gene
- Author
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Kiyoshi Hayasaka, Chance Pf, Masato Himoro, Conneally Pm, Shimizu N, Bird Td, Uyemura K, Wataru Sato, and Goro Takada
- Subjects
Male ,Candidate gene ,Genotype ,Molecular Sequence Data ,Locus (genetics) ,Biology ,Myelin ,Charcot-Marie-Tooth Disease ,Genetics ,medicine ,Humans ,Amino Acid Sequence ,Allele ,Gene ,Alleles ,Base Sequence ,Myelin protein zero ,Point mutation ,Molecular biology ,Pedigree ,Charcot-Marie-Tooth Disease Type 1B ,medicine.anatomical_structure ,Genes ,Chromosomes, Human, Pair 1 ,Mutation ,Female ,Lod Score ,Myelin P0 Protein ,Myelin Proteins ,Polymorphism, Restriction Fragment Length - Abstract
P0, a major structural protein of peripheral myelin, is a homophilic adhesion molecule and maps to chromosome 1q22-q23, in the region of the locus for Charcot-Marie-Tooth neuropathy type 1B (CMT1B). We have investigated P0 as a candidate gene in two pedigrees with CMT1B and found point mutations which are completely linked with the disease (Z = 5.5, theta = 0). The mutations, glutamate substitution for lysine 96 or aspartate 90, are located in the extracellular domain, which plays a significant role in myelin membrane adhesion. Individuals with CMT1B are heterozygous for the normal allele and the mutant allele. Our results indicate that P0 is a gene responsible for CMT1B.
- Published
- 1993