Article: Mutations in a gene encoding a novel protein tyrosine phosphatase cause progressive myoclonus epilepsy

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TitleMutations in a gene encoding a novel protein tyrosine phosphatase cause progressive myoclonus epilepsy
AuthorsMinassian, BA7 9
Lee Jeffrey, R7
Herbrick, JA7
Huizenga, J7
Soder, S7
Mungall, AJ3
Dunham, I3
Gardner, R1
Fong, CYG2
Carpenter, S7
Jardim, L6
Satishchandra, P4
Andermann, E8
Carter Snead III, O9
LopesCendes, I5 8
Tsui, LC7
DelgadoEscueta, AV2
Rouleau, GA5 8
Scherer, SW7
Issue Date1998
PublisherNature Publishing Group. The Journal's web site is located at http://www.genetics.nature.com
CitationNature Genetics, 1998, v. 20 n. 2, p. 171-174 [How to Cite?]
DOI: http://dx.doi.org/10.1038/2470
AbstractLafora'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 symptoms1,2. With few exceptions, patients follow a homogeneous clinical course despite the existence of genetic heterogeneity3. Biopsy of various tissues, including brain, revealed characteristic polyglucosan inclusions called Lafora bodies4-8, which suggested LD might be a generalized storage disease6,9. 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.
ISSN1061-4036
2011 Impact Factor: 35.532
2011 SCImago Journal Rankings: 8.923
DOIhttp://dx.doi.org/10.1038/2470
ISI Accession Number IDWOS:000076231300019
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorMinassian, BA
dc.contributor.authorLee Jeffrey, R
dc.contributor.authorHerbrick, JA
dc.contributor.authorHuizenga, J
dc.contributor.authorSoder, S
dc.contributor.authorMungall, AJ
dc.contributor.authorDunham, I
dc.contributor.authorGardner, R
dc.contributor.authorFong, CYG
dc.contributor.authorCarpenter, S
dc.contributor.authorJardim, L
dc.contributor.authorSatishchandra, P
dc.contributor.authorAndermann, E
dc.contributor.authorCarter Snead III, O
dc.contributor.authorLopesCendes, I
dc.contributor.authorTsui, LC
dc.contributor.authorDelgadoEscueta, AV
dc.contributor.authorRouleau, GA
dc.contributor.authorScherer, SW
dc.date.accessioned2007-09-12T03:51:47Z
dc.date.available2007-09-12T03:51:47Z
dc.date.issued1998
dc.description.abstractLafora'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 symptoms1,2. With few exceptions, patients follow a homogeneous clinical course despite the existence of genetic heterogeneity3. Biopsy of various tissues, including brain, revealed characteristic polyglucosan inclusions called Lafora bodies4-8, which suggested LD might be a generalized storage disease6,9. 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.
dc.description.natureabstract
dc.identifier.citationNature Genetics, 1998, v. 20 n. 2, p. 171-174 [How to Cite?]
DOI: http://dx.doi.org/10.1038/2470
dc.identifier.citeulike3892052
dc.identifier.doihttp://dx.doi.org/10.1038/2470
dc.identifier.epage174
dc.identifier.isiWOS:000076231300019
dc.identifier.issn1061-4036
2011 Impact Factor: 35.532
2011 SCImago Journal Rankings: 8.923
dc.identifier.issue2
dc.identifier.openurl
dc.identifier.pmid9771710
dc.identifier.scopuseid_2-s2.0-17344362307
dc.identifier.spage171
dc.identifier.urihttp://hdl.handle.net/10722/44343
dc.identifier.volume20
dc.languageeng
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.genetics.nature.com
dc.publisher.placeUnited States
dc.relation.ispartofNature Genetics
dc.relation.referencesReferences in Scopus
dc.subject.meshChromosomes, human, pair 6
dc.subject.meshEpilepsies, myoclonic - enzymology - genetics
dc.subject.meshMutation
dc.subject.meshProtein-tyrosine-phosphatase - genetics
dc.subject.meshRna, messenger - metabolism
dc.titleMutations in a gene encoding a novel protein tyrosine phosphatase cause progressive myoclonus epilepsy
dc.typeArticle
Author Affiliations
  1. Salisbury District Hospital
  2. David Geffen School of Medicine at UCLA
  3. Wellcome Trust Sanger Institute
  4. National Institute of Mental Health and Neuro Sciences
  5. Montreal General Hospital
  6. Hospital de Clinicas de Porto Alegre
  7. University of Toronto
  8. McGill University
  9. Hospital for Sick Children, Toronto