Phenotypic and genotypic studies in 6 Chinese Han families with oculopharyngeal muscular dystrophy

Abstract

Objective To explore phenotypes and genotypes in 6 Chinese Han families with oculopharyngeal muscular dystrophy (OPMD).Methods There were 28 OPMD patients in 6 Chinese Han families, aged between 32 and 70 years old.The initial symptom was dysphagia in 13 patients, ptosis in 4 patients,lower limb weakness in 1 patient.Most OPMD patients displayed dysphagia and ptosis in 3-20 years after the initial symptom appeared.Biceps brachii biopsies were made in the 6 OPMD probands.The specimens were examined with histological, histochemical stainings and ultrastructural examination.The exon 1 of PABPN1 gene was sequenced in all probands of OPMD and some of their family members.Haplotype analysis was executed in the 6OPMD probands.Results Mild hypertrophy and hypotrophy of fibers and rimmed vacuoles were found in each probands of OPMD muscle biopsies.Intranuclear palisading filamentous inclusions only appeared in 4OPMD probands.Gene analysis identified (GCG)9 in exon 1 of PA BPN 1 gene was detected in 3OPMD families, while (GCG) 6 (GCA) 1 (GCG) 3, (GCG) 10 and (GCG) 8were in one family respectively.Two families with (GCG) 9 expansion shared a common rs2239579 (C) -(GCG) 9-SNP2622 (C) haplotype.Conclusions Dysphagia and ptosis may be the common initial symptoms in Chinese Han OPMD patients.Rimmed vacuoles and intranuclear inclusions may be the common pathological feature in the muscle fibers.Both (GCG) expansions and (GCA) insertion of PABPN1 gene could be detected in Chinese patients.The genetic heterogeneity and the haplotype of three (GCG)9 families in our patients indicate that OPMD arises from different origin within the Han population.Some families with the same (GCG)9 expansions probably come from a common ancestor. Key words: Muscular dystrophy, oculopharyngeal; Poly(A)-binding protein Ⅱ; Pedigree; Haplotypes