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 journalArticle

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

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Lafora Disease
Protein Tyrosine Phosphatases
Glycogen
Genes
Progressive Myoclonic Epilepsy
Inclusion Bodies
Alternative Splicing
Organism Cloning
Chromosomes
Mutation

ASJC Scopus subject areas

  • Genetics

Cite this

Serratosa, J. M., Gómez-Garre, P., Gallardo, M. E., Anta, B., Beltrán-Valero De Bernabé, D., Lindhout, D., ... Rodríguez De Córdoba, S. (1999). A novel protein tyrosine phosphatase gene is mutated in progressive myoclonus epilepsy of the Lafora type (EPM2). Human Molecular Genetics, 8(2), 345-352. https://doi.org/10.1093/hmg/8.2.345

A novel protein tyrosine phosphatase gene is mutated in progressive myoclonus epilepsy of the Lafora type (EPM2). / Serratosa, José M.; Gómez-Garre, Pilar; Gallardo, Ma Esther; Anta, Berta; Beltrán-Valero De Bernabé, Daniel; Lindhout, Dick; Augustijn, Paul B.; Tassinari, Carlo A.; Michelucci, Roberto; Malafosse, Alain; Topcu, Meral; Grid, Djamel; Dravet, Charlotte; Berkovic, Samuel F.; Rodríguez De Córdoba, Santiago.

In: Human Molecular Genetics, Vol. 8, No. 2, 1999, p. 345-352.

Research output: Contribution to journalArticle

Serratosa, JM, Gómez-Garre, P, Gallardo, ME, Anta, B, Beltrán-Valero De Bernabé, D, Lindhout, D, Augustijn, PB, Tassinari, CA, Michelucci, R, Malafosse, A, Topcu, M, Grid, D, Dravet, C, Berkovic, SF & Rodríguez De Córdoba, S 1999, 'A novel protein tyrosine phosphatase gene is mutated in progressive myoclonus epilepsy of the Lafora type (EPM2)', Human Molecular Genetics, vol. 8, no. 2, pp. 345-352. https://doi.org/10.1093/hmg/8.2.345
Serratosa JM, Gómez-Garre P, Gallardo ME, Anta B, Beltrán-Valero De Bernabé D, Lindhout D et al. A novel protein tyrosine phosphatase gene is mutated in progressive myoclonus epilepsy of the Lafora type (EPM2). Human Molecular Genetics. 1999;8(2):345-352. https://doi.org/10.1093/hmg/8.2.345
Serratosa, José M. ; Gómez-Garre, Pilar ; Gallardo, Ma Esther ; Anta, Berta ; Beltrán-Valero De Bernabé, Daniel ; Lindhout, Dick ; Augustijn, Paul B. ; Tassinari, Carlo A. ; Michelucci, Roberto ; Malafosse, Alain ; Topcu, Meral ; Grid, Djamel ; Dravet, Charlotte ; Berkovic, Samuel F. ; Rodríguez De Córdoba, Santiago. / A novel protein tyrosine phosphatase gene is mutated in progressive myoclonus epilepsy of the Lafora type (EPM2). In: Human Molecular Genetics. 1999 ; Vol. 8, No. 2. pp. 345-352.
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