TY - JOUR
T1 - Novel mutations in EPM2A and NHLRC1 widen the spectrum of Lafora disease
AU - Lesca, Gaetan
AU - Boutry-Kryza, Nadia
AU - de Toffol, Bertrand
AU - Milh, Mathieu
AU - Steschenko, Dominique
AU - Lemesle-Martin, Martine
AU - Maillard, Louis
AU - Foletti, Giovanni
AU - Rudolf, Gabrielle
AU - Nielsen, Jørgen Erik
AU - á Rogvi-Hansen, Bjarke
AU - Erdal, Jesper
AU - Mancini, Josette
AU - Thauvin-Robinet, Christel
AU - M'Rrabet, Amel
AU - Ville, Dorothée
AU - Szepetowski, Pierre
AU - Raffo, Emmanuel
AU - Hirsch, Edouard
AU - Ryvlin, Philippe
AU - Calender, Alain
AU - Genton, Pierre
PY - 2010/9/1
Y1 - 2010/9/1
N2 - 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.
AB - 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.
U2 - 10.1111/j.1528-1167.2010.02692.x
DO - 10.1111/j.1528-1167.2010.02692.x
M3 - Journal article
SN - 0013-9580
VL - 51
SP - 1691
EP - 1698
JO - Epilepsia
JF - Epilepsia
IS - 9
ER -