CONFIRMATION OF LINKAGE OF OCULOPHARYNGEAL MUSCULAR-DYSTROPHY TO CHROMOSOME 14Q11.2-Q13 IN AMERICAN FAMILIES SUGGESTS THE EXISTENCE OF A 2ND-CAUSAL MUTATION

Oculopharyngeal muscular dystrophy (OPMD) is a late-onset, autosomal d ominant disorder characterized by progressive ptosis, dysphagia, and e xtremity weakness. Linkage of OPMD to 14q11.2-q13 has been reported in a series of French-Canadian families. Tightly linked markers have bee n defined and haplotype analysis in these data show a single segregati ng 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 an cestry while the fifth is of English/Scottish origin. Linkage analysis was performed using standard likelihood methods. A peak multipoint lo d score of 6.30 was obtained for the marker MYH7.1 in the OPMD familie s. The English/Scottish family exhibited a different chromosomal haplo type for the OPMD alleles than the families of French-Canadian origin. These data suggest this family may represent a second, possibly indep endent mutation in this disorder. Linkage was confirmed to chromosome 14q11.2-q13 with no evidence of genetic heterogeneity. (C) 1997 Elsevi er Science B.V.