Study of a Taiwanese family with oculopharyngeal muscular dystrophy

Background: Oculopharyngeal muscular dystrophy (OPMD) is a late onset autosomal dominant muscle disorder. OPMD is caused by a short trinucleotide repeat expansion encoding an expanded polyalanine tract in the polyadenylate binding-protein nuclear 1 (PABPN1) gene. We identified and characterized a PABPN1 mutation in a Taiwanese family with OPMD. Methods: The phenotypic and genotypic characteristics of all subjects were evaluated in a Taiwanese OPMD family. Genetic alterations in the PABPN1 gene were identified using PCR and DNA sequencing. Results: Ten subjects with OPMD (6 symptomatic and 4 asymptomatic) within the Taiwanese family carried a novel mutation in the PABPN1 gene. The normal (GCG)₆(GCA)₃GCG sequence was replaced by (GCG)₆(GCA)(GCG)₄(GCA)₃GCG due to an insertion of (GCG)₄GCA into the normal allele in the Taiwanese OPMD subjects. Conclusions: In contrast to a single GCG expansion in most of OPMD patients in the literature, an insertion of (GCG)₄GCA in the PABPN1 gene was found in the Taiwanese OPMD subjects. The identification of this mutation appears to support the molecular mechanism of unequal cross-over of two PABPN1 alleles.