A novel protein tyrosine phosphatase gene is mutated in progressive myoclonus epilepsy of the Lafora type (EPM2)

José M. Serratosa, Pilar Gómez-Garre, Ma Esther Gallardo, Berta Anta, Daniel Beltrán-Valero De Bernabé, Dick Lindhout, Paul B. Augustijn, Carlo A. Tassinari, Roberto Michelucci, Alain Malafosse, Meral Topcu, Djamel Grid, Charlotte Dravet, Samuel F. Berkovic, Santiago Rodríguez De Córdoba

Research output: Contribution to journalArticlepeer-review

Abstract

Progressive myoclonus epilepsy of the Lafora type or Lafora disease (EPM2; McKusick no. 254780) is an autosomal recessive disorder characterized by epilepsy, myoclonus, progressive neurological deterioration and glycogen-like intracellular inclusion bodies (Lafora bodies). A gene for EPM2 previously has been mapped to chromosome 6q23-q25 using linkage analysis and homozygosity mapping. Here we report the positional cloning of the 6q EPM2 gene. A microdeletion within the EPM2 critical region, present in homozygosis in an affected individual, was found to disrupt a novel gene encoding a putative protein tyrosine phosphatase (PTPase). The gene, denoted EPM2, presents alternative splicing in the 5' and 3' end regions. Mutational analysis revealed that EPM2 patients are homozygous for loss-of-function mutations in EPM2. These findings suggest that Lafora disease results from the mutational inactivation of a PTPase activity that may be important in the control of glycogen metabolism.

Original languageEnglish
Pages (from-to)345-352
Number of pages8
JournalHuman Molecular Genetics
Volume8
Issue number2
DOIs
Publication statusPublished - 1999

ASJC Scopus subject areas

  • Genetics

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