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 ; de Bernabé, Daniel Beltrán-Valero ; Lindhout, Dick ; Augustijn, Paul B. ; Tassinari, Carlo A. ; Michelucci, Roberto ; Malafosse, Alain ; Topcu, Meral ; Grid, Djamel ; Dravet, Charlotte ; Berkovic, Samuel F. ; de Córdoba, Santiago Rodríguez
In: Human Molecular Genetics, 1999, vol. 8, no. 2, p. 345-352
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- 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 microeletion 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