GCG genetic expansions in Italian patients with oculopharyngeal muscular dystrophy

Objective: To screen Italian patients with oculopharyngeal muscular dystrophy (OPMD) for GCG repeat expansions in the Poly(A) binding-protein 2 (PABPB) gene. Background: Oculopharyngeal muscular dystrophy is an adult-onset autosomal dominant muscle disease linked to 14q11 pathologically characterized by unique 8.5 nm intranuclear filaments in skeletal muscle fibers. Short expansions of a (GCG)(6) repeat located in exon 1 of the newly isolated PABP2 gene have been demonstrated in a large number of OPMD families. Methods: We studied 18 patients diagnosed with OPMD. A muscle biopsy was performed in 16 patients. Screening for the pathologic expansion was performed on a PCR amplified DNA fragment encompassing the GCG repeat. Results: Heterozygous (GCG)-repeat expansions were detected in 13 patients in association with (GCG)(6) normal allele or (GCG)(7) polymorphic allele. All the patients whose muscle biopsy showed typical 8.5 nm intranuclear filaments had a mutated PABP2 allele. Five patients with no intranuclear filaments were homozygous for the normal (GCG)(6) allele. The pathologic expansion appeared to be stable with no variation among family members and between different tissues as blood and skeletal muscle in the same individual. Conclusions: These data 1) further confirm PABPB gene analysis as a valuable tool in OPMD diagnosis; 2) indicate that PABP2 gene mutations are always present among Italian patients with morphologically proven OPMD, suggesting genetic homogeneity of the disease; and 3) strengthen the putative role of mutated PABP2 protein in filamentous inclusions accumulation.