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.


OBJECTIVE
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.
Department of Neurology, Hillel Yaffe Medical Center, Hadera, Israel. navabl@hotmail.com
Sergiu C
SC
Blumen
Neuro-Ophthalmology Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Anat
A
Kesler
Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel.
Ron
R
Dabby
Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Stavit
S
Shalev
Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Morad
M
Khayat
Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel.
Yechoshua
Y
Almog
Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel.
Joseph
J
Zoldan
Department of Neurology, Rabin Medical Center (Beilinson Campus), Petah Tikva, Israel.
Felix
F
Benninger
Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel.
Vivian E
VE
Drory
Multiple Sclerosis Unit, Sheba Medical Center, Tel Hashomer, Israel.
Michael
M
Gurevich
Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel.
Menachem
M
Sadeh
CENUM, CRCHUM, University of Montreal, Montreal, Canada.
Bernard
B
Brais
Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Itzhak
I
Braverman
D000368:Aged; D002031:Bulgaria / Q000208:ethnology; D004576:Electromyography / Q000379:methods; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007557:Israel / Q000453:epidemiology; D007585:Jews / Q000235:genetics; D008297:Male; D008875:Middle Aged; D018908:Muscle Weakness / Q000175:diagnosis* / Q000503:physiopathology; D039141:Muscular Dystrophy, Oculopharyngeal / Q000208:ethnology / Q000235:genetics / Q000503:physiopathology; D009154:Mutation; D009460:Neurologic Examination / Q000379:methods; D039122:Poly(A)-Binding Protein I / Q000235:genetics*
C576588:PABPN1 protein, human; D039122:Poly(A)-Binding Protein I