title: Linkage and mutation analysis of Charcot-Marie-Tooth neuropathy type 2 families with chromosomes 1p35-p36 and Xq13.
abstract: A locus for autosomal dominant Charcot-Marie-Tooth disease type 2 (CMT2A) was assigned by linkage analysis to chromosome 1p35-p36. We examined 11 unrelated CMT2 families for linkage to CMT2A using short tandem repeat (STR) polymorphisms. Only one family showed suggestive evidence for linkage to 1p35-p36. Further, because of an overlap in electrophysiologic data between CMT2 and CMTX female patients, we screened 6 of 11 CMT2 families compatible with dominant X-linkage for mutations in the connexin 32 (Cx32) gene at Xq13. There was a Cx32 mutation in one family, whereas another family showed suggestive evidence for Xq13 linkage upon analysis with STR polymorphisms. Our results suggest that the CMT2A locus is a minor locus for CMT2, additional linkage studies are needed to localize other CMT2 loci, and Cx32 mutations may be the underlying genetic defect in some CMT2 families.
authors.affiliation: Flemish Institute for Biotechnology, Born Bunge Foundation, Department of Biochemistry, Antwerpen, Belgium.
authors.forename: V
authors.initials: V
authors.lastname: Timmerman
authors.forename: P
authors.initials: P
authors.lastname: De Jonghe
authors.forename: P
authors.initials: P
authors.lastname: Spoelders
authors.forename: S
authors.initials: S
authors.lastname: Simokovic
authors.forename: A
authors.initials: A
authors.lastname: Löfgren
authors.forename: E
authors.initials: E
authors.lastname: Nelis
authors.forename: J
authors.initials: J
authors.lastname: Vance
authors.forename: J J
authors.initials: JJ
authors.lastname: Martin
authors.forename: C
authors.initials: C
authors.lastname: Van Broeckhoven
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D017630:Connexins / Q000235:genetics; D004252:DNA Mutational Analysis; D017931:DNA Primers; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D014960:X Chromosome; D000097002:Gap Junction beta-1 Protein
chemical_list: D017630:Connexins; D017931:DNA Primers; D005819:Genetic Markers; D000097002:Gap Junction beta-1 Protein