Linkage studies in Charcot-Marie-Tooth disease type 2: evidence that CMT types 1 and 2 are distinct genetic entities.
Charcot-Marie-Tooth disease (CMT), the most common inherited peripheral neuropathy, is a progressive sensorimotor neuropathy divided into types 1 and 2 based upon electrophysiologic and neuropathologic differences. The more common autosomal dominant form of CMT type 1 (hereditary motor and sensory neuropathy type I) is genetically heterogeneous, with genes located on chromosomes 1 (type 1B) or 17 (type 1A). However, no locus for CMT type 2 is known. We have performed linkage studies on three large multigenerational CMT type 2 families using probes from chromosome 1 and chromosome 17, which span their respective linkage regions. Multipoint analysis of the chromosome 17 markers excluded linkage over an area of 45 cM--15 cM proximal and 30 cM distal to the region containing CMT type 1A. Multipoint analysis of the chromosome 1 markers exclude linkage 15 cM proximal and 20 cM distal to FC-gamma-RII in the region of CMT 1B. These data indicate that CMT type 2 is genetically distinct from CMT type 1.
Loprest
L J
LJ
Department of Medicine, Duke University Medical Center, Durham, NC.
Pericak-Vance
M A
MA
Stajich
J
J
Gaskell
P C
PC
Lucas
A M
AM
Lennon
F
F
Yamaoka
L H
LH
Roses
A D
AD
Vance
J M
JM
D000293:Adolescent; D000328:Adult; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000503:physiopathology; D010375:Pedigree; D010525:Peripheral Nerves / Q000503:physiopathology