HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Correspondence: Submit a response Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Blumen, S. C. Articles by Brais, B. Search for Related Content PubMed PubMed Citation Articles by Blumen, S. C. Articles by Brais, B.

Oculopharyngeal MD among Bukhara Jews is due to a founder (GCG)9 mutation in the PABP2 gene

From the Department of Neurology (Drs. Blumen, Nisipeanu, Inzelberg, and Carasso), Hillel Yaffe Medical Center, Hadera, Israel; the Rappaport Faculty of Medicine (Drs. Blumen and Inzelberg), The Technion, Haifa, Israel; the Department of Neurology (Drs. Korczyn, Chapman, and Asherov), Tel Aviv Medical Center, Tel Aviv, Israel; the Sieratzki Chair of Neurology (Dr. Korczyn), Tel Aviv University, Ramat Aviv, Israel; the Centre de Recherche du CHUM (Drs. Lavoie and Brais), Université de Montréal, Montreal, Quebec, Canada; the Centre for Research in Neurosciences (Drs. Medynski, Rouleau, and Brais), McGill University Health Center, Montreal, Quebec, Canada; the Departement des Sciences Neurologiques (Dr. Bouchard), Hôpital de l’Enfant-Jésus, Quebec, Canada; and INSERM (Dr. Tomé), Unité 523, Institut de Myologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.

Address correspondence and reprint requests to Dr. S.C. Blumen, Department of Neurology, Hillel Yaffe Medical Center, PO Box 169, Hadera, 38100 Israel; e-mail: neurology{at}hillel-yaffe.health.gov.il

OBJECTIVE: To determine whether all cases of oculopharyngeal muscular dystrophy (OPMD) among Bukhara Jews share the same founder mutation.

BACKGROUND: Autosomal dominant OPMD is caused by a (GCG)_8–13 repeat expansion in the polyadenylation binding protein 2 (PABP2) gene. The disease has a worldwide distribution but is particularly prevalent in Bukhara Jews and in French Canadians, in whom it was introduced by three sisters in 1648.

METHODS: We established the size of the PABP2 mutation in 23 Bukhara Jewish patients belonging to eight unrelated families. In all families, we constructed haplotypes for the carrying chromosomes composed of the alleles for eight chromosome 14q polymorphic markers.

RESULTS: All patients share a (GCG)₉ PABP2 mutation and a four-marker haplotype. Furthermore, a shared intron single nucleotide polymorphism (SNP) in the PABP2 gene 2.6Kb from the mutation was not observed in 22 families with (GCG)₉ mutations from nine different countries. The smaller size of the chromosomal region in linkage disequilibrium around the mutation in Bukhara Jews, as compared with French Canadians, suggests a founder effect that occurred more than 350 years ago. Based on the Luria–Delbrück corrected "genetic clock," we estimate that the mutation appeared or was introduced once in the Bukhara Jewish population between AD 872 and 1512 (mean, AD 1243).

CONCLUSION: OPMD among Bukhara Jews is the result of a shared, historically distinct, PABP2 (GCG)₉ mutation that likely arose or was introduced in this population at the time they first settled in Bukhara and Samarkand during the 13th or 14th centuries.

This article has been cited by other articles:

				S. C. Blumen, J. -P. Bouchard, B. Brais, R. L. Carasso, D. Paleacu, V. E. Drory, S. Chantal, N. Blumen, and I. Braverman Cognitive impairment and reduced life span of oculopharyngeal muscular dystrophy homozygotes Neurology, August 25, 2009; 73(8): 596 - 601. [Abstract] [Full Text] [PDF]

				D Rivera, H Mejia-Lopez, E N Pompa-Mera, C Villanueva-Mendoza, A Nava-Castaneda, L Garnica-Hayashi, S Cuevas-Covarrubias, and J C Zenteno Two different PABPN1 expanded alleles in a Mexican population with oculopharyngeal muscular dystrophy arising from independent founder effects Br J Ophthalmol, July 1, 2008; 92(7): 998 - 1002. [Abstract] [Full Text] [PDF]

				H. Hino, K. Araki, E. Uyama, M. Takeya, M. Araki, K. Yoshinobu, K. Miike, Y. Kawazoe, Y. Maeda, M. Uchino, et al. Myopathy phenotype in transgenic mice expressing mutated PABPN1 as a model of oculopharyngeal muscular dystrophy Hum. Mol. Genet., January 15, 2004; 13(2): 181 - 190. [Abstract] [Full Text] [PDF]

				X. Fan, P. Dion, J. Laganiere, B. Brais, and G. A. Rouleau Oligomerization of polyalanine expanded PABPN1 facilitates nuclear protein aggregation that is associated with cell death Hum. Mol. Genet., October 1, 2001; 10(21): 2341 - 2351. [Abstract] [Full Text] [PDF]