title: Autosomal dominant distal spinal muscular atrophy type V (dSMA-V) and Charcot-Marie-Tooth disease type 2D (CMT2D) segregate within a single large kindred and map to a refined region on chromosome 7p15.
abstract: Two separate disorders, autosomal dominant distal spinal muscular atrophy type V (dSMA-V) characterized by marked bilateral weakness in the hands and atrophy of thenar eminence and the first interosseous muscle, and Charcot-Marie-Tooth disease type 2D (CMT2D) characterized by sensory deficits in addition to the upper limb weakness and wasting, have been independently linked to chromosome 7p. We identified a multigenerational Mongolian kindred with 17 members affected with either dSMA-V or CMT2D and mapped both syndromes to the same region on chromosome 7p15. A maximum two-point lod score of 4.74 at recombination fraction zero was obtained with marker D7S474. Tight linkage without recombination was also detected with markers D7S526 and D7S632. A multipoint lod score of 6.07 suggested that the gene is located between markers D7S526 and D7S474. A single conserved haplotype was associated with dSMA-V and CMT2D. Based on informative recombination events, the disease locus was placed between markers D7S516 and D7S1514 within the 7p15 band. Data obtained from this study suggest that a single gene is responsible for both syndromes, dSMA-V and CMT2D, and extend our knowledge of the candidate region.
authors.affiliation: Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA.
authors.forename: N
authors.initials: N
authors.lastname: Sambuughin
authors.forename: K
authors.initials: K
authors.lastname: Sivakumar
authors.forename: B
authors.initials: B
authors.lastname: Selenge
authors.forename: H S
authors.initials: HS
authors.lastname: Lee
authors.forename: D
authors.initials: D
authors.lastname: Friedlich
authors.forename: D
authors.initials: D
authors.lastname: Baasanjav
authors.forename: M C
authors.initials: MC
authors.lastname: Dalakas
authors.forename: L G
authors.initials: LG
authors.lastname: Goldfarb
mesh_terms: D000328:Adult; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D002874:Chromosome Mapping; D020090:Chromosome Segregation; D002897:Chromosomes, Human, Pair 7; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009134:Muscular Atrophy, Spinal / Q000235:genetics*; D010375:Pedigree