title: Confirmation of linkage of oculopharyngeal muscular dystrophy to chromosome 14q11.2-q13 in American families suggests the existence of a second causal mutation.
abstract: Oculopharyngeal muscular dystrophy (OPMD) is a late-onset, autosomal dominant disorder characterized by progressive ptosis, dysphagia, and extremity weakness. Linkage of OPMD to 14q11.2-q13 has been reported in a series of French-Canadian families. Tightly linked markers have been defined and haplotype analysis in these data show a single segregating disease chromosome throughout the OPMD French-Canadian families. We have ascertained and sampled five multigenerational outbred American OPMD families. Four of the five families have known French-Canadian ancestry while the fifth is of English/Scottish origin. Linkage analysis was performed using standard likelihood methods. A peak multipoint lod score of 6.30 was obtained for the marker MYH7.1 in the OPMD families. The English/ Scottish family exhibited a different chromosomal haplotype for the OPMD alleles than the families of French-Canadian origin. These data suggest this family may represent a second, possibly independent mutation in this disorder. Linkage was confirmed to chromosome 14q11.2-q13 with no evidence of genetic heterogeneity.
authors.affiliation: Division of Neurology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Stajich
authors.forename: J M
authors.initials: JM
authors.lastname: Gilchrist
authors.forename: F
authors.initials: F
authors.lastname: Lennon
authors.forename: A
authors.initials: A
authors.lastname: Lee
authors.forename: L
authors.initials: L
authors.lastname: Yamaoka
authors.forename: B
authors.initials: B
authors.lastname: Rosi
authors.forename: P C
authors.initials: PC
authors.lastname: Gaskell
authors.forename: M
authors.initials: M
authors.lastname: Pritchard
authors.forename: L
authors.initials: L
authors.lastname: Donald
authors.forename: A D
authors.initials: AD
authors.lastname: Roses
authors.forename: J M
authors.initials: JM
authors.lastname: Vance
authors.forename: M A
authors.initials: MA
authors.lastname: Pericak-Vance
mesh_terms: D000328:Adult; D017668:Age of Onset; D002883:Chromosomes, Human, Pair 14; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009136:Muscular Dystrophies / Q000235:genetics*; D009154:Mutation; D009801:Oculomotor Muscles; D010375:Pedigree; D010609:Pharyngeal Muscles; D014481:United States