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Novel cystatin B mutation and diagnostic PCR assay in an unverricht-lundborg progressive myoclonus epilepsy patient

✍ Scribed by Bespalova, Irina N.; Adkins, Steve; Pranzatelli, Michael; Burmeister, Margit


Publisher
John Wiley and Sons
Year
1997
Tongue
English
Weight
27 KB
Volume
74
Category
Article
ISSN
0148-7299

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✦ Synopsis


Two mutations in the cystatin B gene, a 3 splice mutation and a stop codon mutation, were previously found in patients with progressive myoclonus epilepsy of Unverricht-Lundborg type [Pennacchio et al. (1996): Science 271:1731-1734]. We present here a new mutation 2404⌬TC: a 2-bp deletion within the third exon of the cystatin B gene in an Unverricht-Lundborg patient. This mutation results in a frameshift and consequently premature termination of protein synthesis. Complete sequencing of the coding region and splice junctions of the cystatin B gene showed that neither of the two previously known mutations was present in this patient. The level of cystatin B mRNA in an immortalized cell line was found to be decreased, as had been reported for other Unverricht-Lundborg patients. The new mutation further supports the argument that defects in the cystatin B gene cause the Unverricht-Lundborg form of progressive myoclonus epilepsy. We describe a simple PCR method which can detect the 2404⌬TC deletion. This assay, together with previously described PCR assays for the other two known mutations, should prove useful in confirming clinically difficult diagnoses of Unverricht-Lundborg disease. Am. J. Med. Genet. 74:467-471, 1997.