Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027066 (myoclonus)
 4,275 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 inhomozygosis 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.
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PMID:A novel protein tyrosine phosphatase gene is mutated in progressive myoclonus epilepsy of the Lafora type (EPM2). 993 43

Progressive myoclonus epilepsy of the Lafora type (Lafora disease) is an autosomal recessive disease characterised by epilepsy, myoclonus, progressive neurological deterioration and the presence of glycogen-like intracellular inclusion bodies (Lafora bodies). We recently cloned the major gene for Lafora disease (EPM2A) and characterised the corresponding product, a putative protein tyrosine phosphatase (LAFPTPase). Here we report the complete coding sequence of the EPM2A gene and the analysis of this gene in 68 Lafora disease chromosomes. We describe 11 novel mutations: three missense (F84L, G240S and P301L), one nonsense (Y86stop), three < 40 bp microdeletions (K90fs, Ex1-32bpdel, Ex1-33bpdel), and two deletions affecting the entire exon 1 (Ex1-del1 and Ex1-del2). In addition, we have identified three patients with a null allele in non-exonic microsatellites EPM2A-3 or EPM2A-4, suggesting the presence of two distinct > 3 kb deletions affecting exon 2 (Ex2-del1 and Ex2-del2). Considering these mutations, a total of 25 mutations, 60% of them generating truncations, have been described thus far in the EPM2A gene. In spite of this remarkable allelic heterogeneity, the R241stop EPM2A mutation was found in approximately 40% of the Lafora disease patients. We also report the characterisation of five new microsatellite markers and one SNP in the EPM2A gene and describe the haplotypic associations of alleles at these sites in normal and EPM2A chromosomes. This analysis suggests that both founder effect and recurrence have contributed to the relatively high prevalence of R241stop mutation in Spain. The data reported here represent the first systematic analysis of the mutational events in the EPM2A gene in Lafora disease patients and provide insight into the origin and evolution of the different EPM2A alleles.
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PMID:Mutational spectrum of the EPM2A gene in progressive myoclonus epilepsy of Lafora: high degree of allelic heterogeneity and prevalence of deletions. 1117 83