Advances in the genetics of progressive myoclonus epilepsy

The genetic progressive myoclonus epilepsies (PMEs) are clinically characte rized by the triad of stimulus sensitive myoclonus (segmental lightning lik e muscular jerks), epilepsy (grand mal and absences) and progressive neurol ogic deterioration (dementia, ataxia, and various neurologic signs dependin g on the cause). Etiologically heterogenous, PMEs are rare and mostly autos omal recessive disorders, with the exception of autosomal dominant dentator ubral-pallidoluysian atrophy and mitochondrial encephalomyopathy with ragge d red fibers (MERRF). In the last five years, specific mutations have been defined in Lafora disease (gene for laforin or dual specificity phosphatase in 6q24), Unverricht-Lundborg disease (cystatin B in 21q22.3), Jansky-Biei schowsky ceroid lipofuscinoses (Cl gene for tripeptidyl peptidase 1 in 11q1 5), Finnish variant of late infantile ceroid lipofuscinoses (CLN5 gene in 1 3q21-32 encodes 407 amino acids with two transmembrane helices of unknown f unction), juvenile ceroid lipofuscinoses or Batten disease (CLN3 gene in 16 p encodes 438 amino acid protein of unknown function), a subtype of Batten disease and infantile ceroid lipofuscinoses of the Haltia-Santavuori type ( both are caused by mutations in palmitoyl-protein thiosterase gene at 1p32) , dentadorubropallidoluysian atrophy (CAG repeats in a gene in 12p13.31) an d the mitochondrial syndrome MERRF (tRNA Lys mutation in mitochondrial DNA) . In this review, we cover mainly these rapid advances. (C) 2001 Wiley-Liss , Inc.