Abstract:
:Lafora's disease (LD; OMIM 254780) is an autosomal recessive form of progressive myoclonus epilepsy characterized by seizures and cumulative neurological deterioration. Onset occurs during late childhood and usually results in death within ten years of the first symptoms. With few exceptions, patients follow a homogeneous clinical course despite the existence of genetic heterogeneity. Biopsy of various tissues, including brain, revealed characteristic polyglucosan inclusions called Lafora bodies, which suggested LD might be a generalized storage disease. Using a positional cloning approach, we have identified at chromosome 6q24 a novel gene, EPM2A, that encodes a protein with consensus amino acid sequence indicative of a protein tyrosine phosphatase (PTP). mRNA transcripts representing alternatively spliced forms of EPM2A were found in every tissue examined, including brain. Six distinct DNA sequence variations in EPM2A in nine families, and one homozygous microdeletion in another family, have been found to cosegregate with LD. These mutations are predicted to cause deleterious effects in the putative protein product, named laforin, resulting in LD.
journal_name
Nat Genetjournal_title
Nature geneticsauthors
Minassian BA,Lee JR,Herbrick JA,Huizenga J,Soder S,Mungall AJ,Dunham I,Gardner R,Fong CY,Carpenter S,Jardim L,Satishchandra P,Andermann E,Snead OC 3rd,Lopes-Cendes I,Tsui LC,Delgado-Escueta AV,Rouleau GA,Scherer SWdoi
10.1038/2470subject
Has Abstractpub_date
1998-10-01 00:00:00pages
171-4issue
2eissn
1061-4036issn
1546-1718journal_volume
20pub_type
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