The gene for the peripheral myelin protein PMP-22 is a candidate for Charcot-Marie-Tooth disease type 1A.
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.
Patel
P I
PI
Institute for Molecular Genetics, Baylor College of Medicine, Houston, Texas 77030.
Roa
B B
BB
Welcher
A A
AA
Schoener-Scott
R
R
Trask
B J
BJ
Pentao
L
L
Snipes
G J
GJ
Garcia
C A
CA
Francke
U
U
Shooter
E M
EM
Lupski
J R
JR
Suter
U
U
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
D009185:Myelin Proteins; C073687:PMP22 protein, human; C489545:Pmp22 protein, mouse; D004247:DNA