Objective: To screen Italian patients with oculopharyngeal muscular dystrop
hy (OPMD) for GCG repeat expansions in the Poly(A) binding-protein 2 (PABPB
) gene. Background: Oculopharyngeal muscular dystrophy is an adult-onset au
tosomal dominant muscle disease linked to 14q11 pathologically characterize
d 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 PAB
P2 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 P
CR amplified DNA fragment encompassing the GCG repeat. Results: Heterozygou
s (GCG)-repeat expansions were detected in 13 patients in association with
(GCG)(6) normal allele or (GCG)(7) polymorphic allele. All the patients who
se 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 st
able with no variation among family members and between different tissues a
s blood and skeletal muscle in the same individual. Conclusions: These data
1) further confirm PABPB gene analysis as a valuable tool in OPMD diagnosi
s; 2) indicate that PABP2 gene mutations are always present among Italian p
atients with morphologically proven OPMD, suggesting genetic homogeneity of
the disease; and 3) strengthen the putative role of mutated PABP2 protein
in filamentous inclusions accumulation.