P.16.13 Myopathy with typical OPMD morphology without association with the PABPN1 gene locus

Abstract

Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset disease characterized by progressive ptosis of the eyelids and dysphagia. Intranuclear inclusions of tubulofilamentous (INIs) in skeletal muscle constitute a pathological hallmark for this disease. The filaments are up to 250 nm in length and have external diameter of 8.5 nm and an internal diameter of 3 nm. The only causative mutation described to date is a triplet repeat expansion consisting of 2–7 additional base triplets in a repeat sequence in exon 1 of the polyadenine binding protein nuclear 1 (PABPN1) gene localized on chromosome 14q11.2. This results in an increase in length of a polyalanine tract in the PABPN1 protein from 10 to 12–17 residues. We describe the clinical, histopathological and genetically findings in three individuals from a Swedish family, with a dominantly inherited adult-onset myopathy characterized by ptosis and dysphagia. Muscle histopathological features included rimmed vacuoles and nuclei containing inclusions of unique 8.5 nm filaments and insoluble PABPN1 protein. The PABPN1 gene was excluded as the disease causative gene in this family both by direct DNA sequencing of the gene together with high density single nucleotide polymorphism (SNP) arrays covering the entire genome excluding the locus harbouring the PABPN1 gene.