Novel mutations in EPM2A and NHLRC1 widen the spectrum of Lafora disease

Details

Serval ID
serval:BIB_745824DA8E0C
Type
Article: article from journal or magazin.
Collection
Publications
Title
Novel mutations in EPM2A and NHLRC1 widen the spectrum of Lafora disease
Journal
Epilepsia
Author(s)
Lesca G., Boutry-Kryza N., de Toffol B., Milh M., Steschenko D., Lemesle-Martin M., Maillard L., Foletti G., Rudolf G., Nielsen J. E., a Rogvi-Hansen B., Erdal J., Mancini J., Thauvin-Robinet C., M'Rrabet A., Ville D., Szepetowski P., Raffo E., Hirsch E., Ryvlin P., Calender A., Genton P.
ISSN
1528-1167 (Electronic)
ISSN-L
0013-9580
Publication state
Published
Issued date
09/2010
Volume
51
Number
9
Pages
1691-8
Language
english
Notes
Lesca, Gaetan
Boutry-Kryza, Nadia
de Toffol, Bertrand
Milh, Mathieu
Steschenko, Dominique
Lemesle-Martin, Martine
Maillard, Louis
Foletti, Giovanni
Rudolf, Gabrielle
Nielsen, Jorgen Erik
a Rogvi-Hansen, Bjarke
Erdal, Jesper
Mancini, Josette
Thauvin-Robinet, Christel
M'Rrabet, Amel
Ville, Dorothee
Szepetowski, Pierre
Raffo, Emmanuel
Hirsch, Edouard
Ryvlin, Philippe
Calender, Alain
Genton, Pierre
eng
Comparative Study
Epilepsia. 2010 Sep;51(9):1691-8. doi: 10.1111/j.1528-1167.2010.02692.x. Epub 2010 Aug 5.
Abstract
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.
Keywords
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
Pubmed
Create date
29/11/2018 13:36
Last modification date
20/08/2019 15:32
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