Abstract

Background: Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant late onset neuromuscular disease characterised by proximal muscle weakness, ptosis, and swallowing difficulty. The only causative mutation described to date is a triplet repeat expansion consisting of two to seven additional base triplets in a repeat sequence in exon 1 of the polyadenine binding protein nuclear 1 (PABPN1) gene. This results in an increase in length of a polyalanine tract in the PABPN1 protein from 10 to 12–17 residues.

Objective: Description of another mutation in a case of OPMD.

Methods: Sequence analysis of exon 1 of the PABPN1 gene was undertaken on 202 patients referred for a possible diagnosis of OPMD but negative for the triplet repeat expansion mutation.

Results: A case was identified with typical symptoms of OPMD, negative for the repeat expansion mutation but with a missense mutation in PABPN1 close to the 3′ end of the normal polyalanine codon repeat sequence.

Conclusions: The single base mutation changes a glycine codon to an alanine codon and results in an increase in the number of contiguous polyalanine codons. This mimics the effect of the common triplet repeat expansion mutation and represents a previously undescribed mechanism of mutation.