Oculopharyngeal muscular dystrophy among Bulgarian Jews: a new cluster?

BACKGROUND

Oculopharyngeal muscular dystrophy (OPMD) produced by the (GCG)13 expansion mutation in the PABPN1 gene is frequent among Uzbek Jews in Israel.

OBJECTIVES

To describe the phenotypic and genotypic features in five Bulgarian Jewish patients, from different families, with autosomal dominant OPMD.

METHODS

We performed clinical follow-up, electrodiagnostic tests and mutation detection. Blood samples were obtained after informed consent and DNA was extracted; measurement of GCG repeats in both PABPN1 alleles and sequencing of OPMD mutations were performed according to standard techniques.

RESULTS

We identified five patients (four females), aged 58 to 71 years, with bilateral ptosis, dysphagia, dysphonia (n = 3) and myopathic motor units by electromyography. In all patients we noticed proximal weakness of the upper limbs with winging scapulae in three of them. All cases shared the (GCG)13-(GCG)10 PABPN1 genotype.

CONCLUSIONS

OPMD among Bulgarian Jews is produced by a (GCG)13 expansion, identical to the mutation in Uzbek Jews and French Canadians. In addition to the classical neurological and neuro-ophthalmological features, early shoulder girdle weakness is common in Bulgarian Jewish patients; this is an unusual feature during the early stages of OPMD produced by the same mutation in other populations. We suggest that besides the disease-producing GCG expansion, additional ethnicity-related genetic factors may influence the OPMD phenotype. OPMD is a rare disease, and the identification of five affected families in the rather small Bulgarian Jewish community in Israel probably represents a new cluster; future haplotype studies may elucidate whether a founder effect occurred.