Unverricht-Lundborg disease in a five-generation Arab family: instability of dodecamer repeats.
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.
Mazarib
A
A
Department of Neurology, Tel-Aviv Sourasky Medical Center, Israel.
Xiong
L
L
Neufeld
M Y
MY
Birnbaum
M
M
Korczyn
A D
AD
Pandolfo
M
M
Berkovic
S F
SF
D000328:Adult; D018912:Arabs / Q000235:genetics*; D055313:Cystatin B; D015891:Cystatins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D007178:Inbreeding; D007557:Israel; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D010375:Pedigree; D011401:Promoter Regions, Genetic; D020194:Unverricht-Lundborg Syndrome / Q000175:diagnosis / Q000235:genetics*
C524994:CSTB protein, human; D015891:Cystatins; D055313:Cystatin B