Oculopharyngeal muscular dystrophy (OPMD) due to a small duplication in the PABPN1 gene

Oculopharyngeal muscular dystrophy (OPMD) is a late onset autosomal dominant muscle disorder. The OPMD-locus has been mapped to chromosome 14q11.2-q13. The polyadenylate binding protein nuclear 1 (PABPN1; PABP2) gene has been identified as the mutated gene. The mutation consists of a short meiotically stable trinucleotide repeat in the first exon of PABPN1 gene. We have investigated Dutch OPMD patients from four unrelated families and identified a new mutation in two of the four families. Instead of a repeat expansion we found a duplication in the first exon of the PABPN1 gene (c.27_28ins12, p.11_12insAAAA). The identification of this new mutation supports the theory of unequal crossing-over as molecular mechanism causing the mutation in the PABPN1 gene responsible for OPMD, and not the slippage model.