PABPN1 (GCN)11 as a Dominant Allele in Oculopharyngeal Muscular Dystrophy -Consequences in Clinical Diagnosis and Genetic Counselling

Pascale Richard; Capucine Trollet; Teresa Gidaro; Laurence Demay; Guy Brochier; Edoardo Malfatti; Fernando Ms Tom; Michel Fardeau; Pascal Lafor; Norma Romero; Marie-Laure Martin-N; Guilhem Sol; Xavier Ferrer-Monasterio; Jean Lacau Saint-Guily; Bruno Eymard

doi:10.3233/JND-140060

PABPN1 (GCN)11 as a Dominant Allele in Oculopharyngeal Muscular Dystrophy -Consequences in Clinical Diagnosis and Genetic Counselling

J Neuromuscul Dis. 2015 Jun 4;2(2):175-180. doi: 10.3233/JND-140060.

Affiliations

¹ APHP, Unité Fonctionnelle de Cardiogénétique et Myogénétique Moléculaire et Cellulaire, Service de Biochimie M?bolique, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, 47-83, bld de l'hôpital, Paris cedex 13, France/UMRS 956-UPMC, Paris 6, France.
² Sorbonne Universités, UPMC Univ Paris 06, UM76, INSERM U974, Institut de Myologie, CNRS FRE3617, 47 bd de l'Hôpital,Paris, France.
³ APHP, Unité de Morphologie Neuromusculaire, Pavillon Risler, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Paris, France.
⁴ CHU de Bordeaux, Centre de Référence des Maladies Neuromusculaires, Hôpital Pellegrin, Place Amelie Raba Leon, Bordeaux, France.
⁵ APHP, Service d'ORL et chirurgie cervicofaciale, hôpital Tenon, UPMC Université Paris 6, 4 rue de la Chine, Paris, France.
⁶ APHP, Centre de Référence des Maladies Neuromusculaires Paris Est, Unité de Morphologie Neuromusculaire, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, -83, bld de l'hôpital, Paris cedex 13, France.

Abstract

Oculopharyngeal muscular dystrophy (OPMD) is mainly characterized by ptosis and dysphagia. The genetic cause is a short expansion of a (GCN)10 repeat encoding for polyalanine in the poly(A) binding protein nuclear 1 (PABPN1) gene to (GCN)12-17 repeats. The (GCN)11/Ala11 allele has so far been described to be either a polymorphism or a recessive allele with no effect on the phenotype in the heterozygous state. Here we report the clinical and histopathological phenotype of a patient carrying a single (GCN)11/Ala11 heterozygous allele and presenting an atypical form of OPMD with dysphagia and late and mild oculomotor symptoms. Intranuclear inclusions were observed in his muscle biopsy. This suggests a dominant mode of expression of the (GCN)11/Ala11 allele associated with a partial penetrance of OPMD.

Keywords: Oculopharyngeal muscular dystrophy; PABPN1 gene; genetics.