Document Detail


Novel mutations in EPM2A and NHLRC1 widen the spectrum of Lafora disease.
MedLine Citation:
PMID:  20738377     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: Lafora disease (LD) is an autosomal recessive form of progressive myoclonus epilepsy with onset in childhood or adolescence and with fatal outcome caused by mutations in two genes: EPM2A and NHLRC1. The aim of this study was to characterize the mutation spectrum in a cohort of unrelated patients with presumed LD.
METHODS: Sequencing of the two genes and search for large rearrangements was performed in 46 unrelated patients with suspected LD, 33 originating from France and the others from different countries. Patients were classified into two groups according to the clinical presentation.
RESULTS: Mutations of various types were found in EPM2A in 10 patients and in NHLRC1 in 4 patients. Mutations were found in 14 (93%) of 15 patients with classical clinical and electroencephalography (EEG) presentation of LD and in no patients with an atypical presentation. Ten mutations were novel, including the first substitution reported in a donor splice site of EPM2A, leading to the deletion of exon 2 at the RNA level. Four large deletions, including two deletions of exon 2 with different sizes and breakpoints, were found in EPM2A, corresponding to 20% of the alleles of this gene.
DISCUSSION: We described several novel mutations of EPM2A and NHLRC1 and brought additional data to the genetic epidemiology of LD. This study emphasized the high mutation rate in patients with classical LD as well as the high negativity rate of skin biopsy.
Authors:
Gaetan Lesca; Nadia Boutry-Kryza; Bertrand de Toffol; Mathieu Milh; Dominique Steschenko; Martine Lemesle-Martin; Louis Maillard; Giovanni Foletti; Gabrielle Rudolf; Jørgen Erik Nielsen; Bjarke á Rogvi-Hansen; Jesper Erdal; Josette Mancini; Christel Thauvin-Robinet; Amel M'Rrabet; Dorothée Ville; Pierre Szepetowski; Emmanuel Raffo; Edouard Hirsch; Philippe Ryvlin; Alain Calender; Pierre Genton
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Publication Detail:
Type:  Comparative Study; Journal Article     Date:  2010-08-05
Journal Detail:
Title:  Epilepsia     Volume:  51     ISSN:  1528-1167     ISO Abbreviation:  Epilepsia     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-13     Completed Date:  2010-10-15     Revised Date:  2010-12-17    
Medline Journal Info:
Nlm Unique ID:  2983306R     Medline TA:  Epilepsia     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1691-8     Citation Subset:  IM    
Affiliation:
Service de génétique, hospices civils de Lyon et université Claude Bernard Lyon I, Lyon, France. gaetan.lesca@chu-lyon.fr
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Biopsy
Carrier Proteins / genetics*
Exons / genetics
Female
Genetic Markers / genetics
Humans
Lafora Disease / diagnosis,  genetics*,  pathology
Male
Microsatellite Repeats / genetics
Mutation / genetics*
Pedigree
Protein Tyrosine Phosphatases, Non-Receptor / genetics*
Skin / pathology
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/Genetic Markers; 0/NHLRC1 protein, human; EC 3.1.3.48/Protein Tyrosine Phosphatases, Non-Receptor; EC 3.1.3.48./EPM2A protein, human

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