Confirmation of linkage of oculopharyngeal muscular dystrophy to chromosome 14q11.2-q13 in American families suggests the existence of a second causal mutation.
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.
Stajich
J M
JM
Division of Neurology, Duke University Medical Center, Durham, NC 27710, USA.
Gilchrist
J M
JM
Lennon
F
F
Lee
A
A
Yamaoka
L
L
Rosi
B
B
Gaskell
P C
PC
Pritchard
M
M
Donald
L
L
Roses
A D
AD
Vance
J M
JM
Pericak-Vance
M A
MA
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