Oculopharyngeal muscular dystrophy in a Japanese family with a short GCG expansion (GCG)(11) in PABP2 gene

Clinicopathological and molecular genetic findings on a new Japanese family with oculopharyngeal muscular dystrophy are reported. The family has 54 me mbers, ten of whom are affected (seven male and three female), in 3 generat ions. Three affected males, one affected female and one unaffected female o f seven Living siblings in the third generation were examined. Bilateral pt osis developed in the 4th and 5th decades in the three male cases, and in t he 7th decade in the female, and this was followed by diplopia, nasal voice , dysphagia and muscle weakness. In addition, severe external ophthalmopleg ia, dysphonia, and proximal amyotrophy were prominent in this family. Elect romyographs revealed myogenic/neurogenic changes, and computed tomography d isclosed selective muscle wasting with fatty replacement, predominantly in the lower extremities. Muscle biopsy in the four affected patients showed v ariation in fiber size, and the presence of small angulated fibers and occa sional rimmed vacuoles. Electron microscopic examination revealed an accumu lation of filamentous inclusions in muscle fiber nuclei. DNA analysis ident ified that (GCG)(6) in the PABP2 gene was expanded to (GCG)(11) in the four affected cases examined. All studies were negative in the one unaffected. These results confirm that OPMD is caused by GCG short expansion and provid es insights into the genetic mechanisms which may contribute to adult onset myopathy, confined to oculopharyngeal muscles. (C) 2000 Elsevier Science B .V. All rights reserved.