title: Confirmation of a second locus for CMT2 and evidence for additional genetic heterogeneity.
abstract: The Charcot-Marie-Tooth (CMT) neuropathies are a group of disorders exhibiting neurophysical, pathological and genetic heterogeneity. CMT2 is a diagnostic subtype of this group of disorders characterized by variable expression and age-of-onset and normal or slightly diminished nerve conduction velocities. Previously, linkage and heterogeneity had been reported in CMT2 with linked families localizing to chromosome 1p (CMT2A). Recently a second CMT2 locus has been described on chromosome 7 in a single large CMT2 family (CMT2D). We have performed pedigree linkage analysis on 15 CMT2 families (N = 371 individuals, 106 affected family members) and have confirmed linkage to chromosome 7. Furthermore, using both admixture and multipoint linkage analysis we show conclusive evidence for additional heterogeneity within this clinical subtype with evidence of families that exclude linkage to both the CMT2D and CMT2A regions. In addition, unlike the previous report we found no obvious consistent clinical differences between the linked family types.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC, USA. mpv@locus.mc.duke.edu
authors.forename: M A
authors.initials: MA
authors.lastname: Pericak-Vance
authors.forename: M C
authors.initials: MC
authors.lastname: Speer
authors.forename: F
authors.initials: F
authors.lastname: Lennon
authors.forename: S G
authors.initials: SG
authors.lastname: West
authors.forename: M M
authors.initials: MM
authors.lastname: Menold
authors.forename: J M
authors.initials: JM
authors.lastname: Stajich
authors.forename: C M
authors.initials: CM
authors.lastname: Wolpert
authors.forename: B D
authors.initials: BD
authors.lastname: Slotterbeck
authors.forename: M
authors.initials: M
authors.lastname: Saito
authors.forename: R W
authors.initials: RW
authors.lastname: Tim
authors.forename: M P
authors.initials: MP
authors.lastname: Rozear
authors.forename: L T
authors.initials: LT
authors.lastname: Middleton
authors.forename: S
authors.initials: S
authors.lastname: Tsuji
authors.forename: J M
authors.initials: JM
authors.lastname: Vance
mesh_terms: D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D002874:Chromosome Mapping; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005192:Family Health; D005260:Female; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D010375:Pedigree
chemical_list: D004247:DNA