A unique point mutation in the PMP22 gene is associated with Charcot- Marie-Tooth disease and deafness

Margaret J. Kovach, Jing Ping Lin, Simeon Boyd, Kathleen Campbell, Larry Mazzeo, Kristin Herman, Lisa A. Rimer, William Frank, Barbara Llewellyn, Ethylin Wang Jabs, David Gelber, Virginia E. Kimonis

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


Charcot-Marie-Tooth disease (CMT) with deafness is clinically distinct among the genetically heterogeneous group of CMT disorders. Molecular studies in a large family with autosomal dominant CMT and deafness have not been reported. The present molecular study involves a family with progressive features of CMT and deafness, originally reported by Kousseff et al. Genetic analysis of 70 individuals (31 affected, 28 unaffected, and 11 spouses) revealed linkage to markers on chromosome 17p11.2-p12, with a maximum LOD score of 9.01 for marker D17S1357 at a recombination fraction of .03. Haplotype analysis placed the CMT-deafness locus between markers D17S839 and D17S122, a ~0.6-Mb interval. This critical region lies within the CMT type 1A duplication region and excludes MYO15, a gene coding an unconventional myosin that causes a form of autosomal recessive deafness called DFNB3. Affected individuals from this family do not have the common 1.5Mb duplication of CMT type 1A. Direct sequencing of the candidate peripheral myelin protein 22 (PMP22) gene detected a unique G→C transversion in the heterozygous state in all affected individuals, at position 248 in coding exon 3, predicted to result in an Ala67Pro substitution in the second transmembrane domain of PMP22.

Original languageEnglish (US)
Pages (from-to)1580-1593
Number of pages14
JournalAmerican Journal of Human Genetics
Issue number6
StatePublished - 1999
Externally publishedYes

ASJC Scopus subject areas

  • Genetics


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