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

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

Pascale Richard  1 , Capucine Trollet  2 , Teresa Gidaro  2 , Laurence Demay  1 , Guy Brochier  3 , Edoardo Malfatti  3 , Fernando Ms Tom, Michel Fardeau  3 , Pascal Lafor, Norma Romero  3 , Marie-Laure Martin-N, Guilhem Sol, Xavier Ferrer-Monasterio  4 , Jean Lacau Saint-Guily  5 , Bruno Eymard  6
Affiliations

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

Pascale Richard et al. J Neuromuscul Dis. .

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.

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Figures

Fig.1
Fig.1
A. Electronic microscopy of the quadriceps muscle biopsy showing a central lighter area (see also inset box) with typical tubulo-filamentous inclusions in a nucleus. Magnification x50 000. Scale bars 0.1μm. B. Gomori Trichrome staining revealing the presence of rimmed vacuoles (arrow). Bar scale = 50 μm. C. Hematoxylin and eosin staining showing endomysial connective tissue (asterisk) and internally localised nuclei (around 10% , arrows) and no sign of abnormalities. Bar scale = 50 μm. D and D’. PABPN1 immunostaining following KCl treatment on the sternocleidomastoid muscle biopsy revealing PABPN1 intranuclear inclusions (arrow, see also inset box). Blue, nuclei counterstained with Hoechst; green, PABPN1; red, Dystrophin). The percentage of intranuclear inclusions was 6.9% counted on 463 nuclei of the muscle biopsy. Bar scale = 50 μm.
Fig.2
Fig.2
Electrophoregram of a partial sequence of exon 1 showing the expansion of a triplet (GCN). A simple schematic indicates the single GCG expansion in the mutated allele in the patient (surrounded text and black arrow). The absence of any other mutation that could explain the phenotype has been confirmed by full sequencing of the whole PABPN1 gene (data not shown).
See this image and copyright information in PMC

References

    1. Taylor E. Progressive vagus-glossopharyngeal paralysis with ptosis: A contribution to the group family diseases. J Nerv Ment Dis. 1915. pp. 129–139.
    1. Victor M, Hayes R, Adams RD. Oculopharyngeal muscular dystrophy. A familial disease of late life characterized by dysphagia and progressive ptosis of the evelids. N Engl J Med. 1962;267:1267–1272. - PubMed
    1. Bouchard JP, Brais B, Brunet D, Gould PV, Rouleau GA. Recent studies on oculopharyngeal muscular dystrophy in Quebec. Neuromuscul Disord. 1997;1(Suppl 1):S22–S29. - PubMed
    1. Hill ME, Creed GA, McMullan TF, Tyers AG, Hilton-Jones D, Robinson DO, et al. Oculopharyngeal muscular dystrophy: Phenotypic and genotypic studies in a UK population. Brain. 2001;124(Pt 3):522–526. - PubMed
    1. Witting N, Mensah A, Kober L, Bundgaard H, Petri H, Duno M, et al. Ocular, bulbar, limb, and cardiopulmonary involvement in oculopharyngeal muscular dystrophy. Acta Neurol Scand. 2014;130(2):125–130. - PubMed