title: Evidence for locus heterogeneity in the Bethlem myopathy and linkage to 2q37.
abstract: The Bethlem myopathy, a childhood onset autosomal dominant myopathy with joint contractures, has recently been localized to 21q in a series of Dutch families and the alpha 1 and alpha 2 subunits of type VI collagen (COL6A1 and COL6A2) have been postulated as candidate genes. We investigate a large family of French Canadian descent (family 1489) in which the Bethlem myopathy is segregating. Family 1489 is unlinked to the region of interest on 21q, thus demonstrating locus heterogeneity within the Bethlem myopathy classification. In view of the localization of the genes coding the alpha 1 and alpha 2 subunits of type VI collagen on chromosome 21q, we carried out linkage analysis on chromosome 2q where the alpha 3 subunit of type VI collagen has been localized. We demonstrate linkage to markers in this region, define the region of disease gene localization, and confirm by FISH analysis that COL6A3 is located within the interval of interest making COL6A3 a feasible candidate gene for the Bethlem myopathy.
authors.affiliation: Division of Neurology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Speer
authors.forename: R
authors.initials: R
authors.lastname: Tandan
authors.forename: P N
authors.initials: PN
authors.lastname: Rao
authors.forename: T
authors.initials: T
authors.lastname: Fries
authors.forename: J M
authors.initials: JM
authors.lastname: Stajich
authors.forename: P A
authors.initials: PA
authors.lastname: Bolhuis
authors.forename: G J
authors.initials: GJ
authors.lastname: Jöbsis
authors.forename: J M
authors.initials: JM
authors.lastname: Vance
authors.forename: K D
authors.initials: KD
authors.lastname: Viles
authors.forename: K
authors.initials: K
authors.lastname: Sheffield
authors.forename: C
authors.initials: C
authors.lastname: James
authors.forename: S G
authors.initials: SG
authors.lastname: Kahler
authors.forename: M
authors.initials: M
authors.lastname: Pettenati
authors.forename: J R
authors.initials: JR
authors.lastname: Gilbert
authors.forename: P H
authors.initials: PH
authors.lastname: Denton
authors.forename: L H
authors.initials: LH
authors.lastname: Yamaoka
authors.forename: M A
authors.initials: MA
authors.lastname: Pericak-Vance
mesh_terms: D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D003094:Collagen / Q000235:genetics*; D005260:Female; D005796:Genes / Q000235:genetics; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D008297:Male; D009468:Neuromuscular Diseases / Q000235:genetics*; D010375:Pedigree
chemical_list: D005819:Genetic Markers; D003094:Collagen