title: The gene for the peripheral myelin protein PMP-22 is a candidate for Charcot-Marie-Tooth disease type 1A.
abstract: Charcot-Marie-Tooth disease type 1A (CMT1A) is an autosomal dominant peripheral neuropathy associated with a large DNA duplication on the short arm of human chromosome 17. The trembler (Tr) mouse serves as a model for CMT1A because of phenotypic similarities and because the Tr locus maps to mouse chromosome 11 in a region of conserved synteny with human chromosome 17. Recently, the peripheral myelin gene Pmp-22 was found to carry a point mutation in Tr mice. We have isolated cDNA and genomic clones for human PMP-22. The gene maps to human chromosome 17p11.2-17p12, is expressed at high levels in peripheral nervous tissue and is duplicated, but not disrupted, in CMT1A patients. Thus, we suggest that a gene dosage effect involving PMP-22 is at least partially responsible for the demyelinating neuropathy seen in CMT1A.
authors.affiliation: Institute for Molecular Genetics, Baylor College of Medicine, Houston, Texas 77030.
authors.forename: P I
authors.initials: PI
authors.lastname: Patel
authors.forename: B B
authors.initials: BB
authors.lastname: Roa
authors.forename: A A
authors.initials: AA
authors.lastname: Welcher
authors.forename: R
authors.initials: R
authors.lastname: Schoener-Scott
authors.forename: B J
authors.initials: BJ
authors.lastname: Trask
authors.forename: L
authors.initials: L
authors.lastname: Pentao
authors.forename: G J
authors.initials: GJ
authors.lastname: Snipes
authors.forename: C A
authors.initials: CA
authors.lastname: Garcia
authors.forename: U
authors.initials: U
authors.lastname: Francke
authors.forename: E M
authors.initials: EM
authors.lastname: Shooter
authors.forename: J R
authors.initials: JR
authors.lastname: Lupski
authors.forename: U
authors.initials: U
authors.lastname: Suter
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002607:Charcot-Marie-Tooth Disease / Q000145:classification / Q000235:genetics*; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D051379:Mice; D008818:Mice, Neurologic Mutants; D008969:Molecular Sequence Data; D005810:Multigene Family; D009185:Myelin Proteins / Q000235:genetics*; D010375:Pedigree
chemical_list: D009185:Myelin Proteins; C073687:PMP22 protein, human; C489545:Pmp22 protein, mouse; D004247:DNA