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Unverricht–Lundborg disease in a five-generation Arab family

Instability of dodecamer repeats

From the Department of Neurology (Drs. Mazarib, Neufeld, Birnbaum, and Korczyn), Tel-Aviv Sourasky Medical Center, Israel; the Department of Medicine (Drs. Xiong and Pandolfo), University of Montreal, Hospitalier de l’Université de Montreal, Canada; Tel-Aviv University, Sieratzki Chair of Neurology (Dr. Korczyn), Ramat-Aviv, Israel; and the Epilepsy Research Institute, Austin & Repatriation Medical Center, and the Department of Medicine—Neurology (Dr. Berkovic), University of Melbourne, Australia.

Address correspondence and reprint requests to Dr. Samuel F. Berkovic, Director, Epilepsy Research Institute, Level 1, Neurosciences Building, Austin & Repatriation Medical Center, Banksia Street, West Heidelberg, Victoria 3081, Australia; e-mail: sberko{at}austin.unimelb.edu.au

Background:— Unverricht–Lundborg disease (ULD) is the prototypical form of progressive myoclonus epilepsy, and subjects are usually very photosensitive. ULD is caused by mutations in the cystatin B (CSTB) gene; the most common mutation is expansion of a dodecamer repeat near the promoter. The authors studied a five-generation Arab family with ULD lacking photosensitivity.

Methods:— An Arab family from the Galilee region of Israel with progressive myoclonus epilepsy was clinically evaluated. Blood samples were obtained from three living affected and 16 unaffected individuals. Expansion of dodecamer repeat in the CSTB gene was examined.

Results:— The three living affected individuals showed spontaneous and action myoclonus, ataxia, and mild dementia. EEG in two individuals showed generalized polyspike-wave without photosensitivity. The family structure with large sibships and multiple consanguineous loops allowed the authors to examine the gene over four generations of adults. The three living affected individuals were homozygous for repeat expansions and 11 of the 16 unaffected family members were heterozygous. Instability was demonstrated by the presence of expansions of different sizes occurring on the same haplotype background in this inbred family. Fragment size variations could be unequivocally detected in two sibships. The expansions were in the 49 to 54 dodecamer repeat range. Changes in one generation were small, 1 to 4 repeat units, consisting of either enlargements or contractions.

Conclusions:— Instability of the expanded dodecamer repeats in the cystatin B gene is frequent. Almost invariably, a small change is observed in parent–child transmission. The lack of photosensitivity in this family is unexplained.

This article has been cited by other articles:

				S. F. Berkovic, A. Mazarib, S. Walid, M. Y. Neufeld, J. Manelis, Y. Nevo, A. D. Korczyn, J. Yin, L. Xiong, M. Pandolfo, et al. A new clinical and molecular form of Unverricht-Lundborg disease localized by homozygosity mapping Brain, March 1, 2005; 128(3): 652 - 658. [Abstract] [Full Text] [PDF]