West syndrome caused by homozygous variant in the evolutionary conserved gene encoding the mitochondrial elongation factor GUF1.

Détails

ID Serval
serval:BIB_83BC90BB9FA1
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
West syndrome caused by homozygous variant in the evolutionary conserved gene encoding the mitochondrial elongation factor GUF1.
Périodique
European journal of human genetics
Auteur(s)
Alfaiz A.A., Müller V., Boutry-Kryza N., Ville D., Guex N., de Bellescize J., Rivier C., Labalme A., des Portes V., Edery P., Till M., Xenarios I., Sanlaville D., Herrmann J.M., Lesca G., Reymond A.
ISSN
1476-5438 (Electronic)
ISSN-L
1018-4813
Statut éditorial
Publié
Date de publication
07/2016
Peer-reviewed
Oui
Volume
24
Numéro
7
Pages
1001-1008
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
West syndrome (WS), defined by the triad of infantile spasms, pathognomonic hypsarrhythmia and developmental regression, is a rare epileptic disease affecting about 1:3500 live births. To get better insights on the genetic of this pathology, we exome-sequenced the members of a consanguineous family affected with isolated WS. We identified a homozygous variant (c.1825G>T/p.(Ala609Ser)) in the GUF1 gene in the three affected siblings. GUF1 encodes a protein essential in conditions that counteract faithful protein synthesis: it is able to remobilize stuck ribosomes and transiently inhibit the elongation process to optimize protein synthesis. The variant identified in the WS family changes an alanine residue conserved in all eukaryotic organisms and positioned within the tRNA-binding moiety of this nuclear genome-encoded mitochondrial translational elongation factor. Yeast complementation assays show that the activity of GUF1(A609S) is modified in suboptimal environments. We suggest a new link between improper assembly of respiratory chain complexes and WS.

Mots-clé
Binding Sites, Conserved Sequence, Exome, Female, GTP Phosphohydrolases/genetics, GTP Phosphohydrolases/metabolism, Genetic Complementation Test, Homozygote, Humans, Infant, Male, Mitochondrial Proteins/genetics, Mitochondrial Proteins/metabolism, Mutation, Missense, Pedigree, Peptide Elongation Factor 1, Peptide Elongation Factor G/genetics, Peptide Elongation Factor G/metabolism, Protein Binding, Spasms, Infantile/genetics, Spasms, Infantile/pathology, Yeasts/genetics
Pubmed
Web of science
Création de la notice
07/01/2016 17:56
Dernière modification de la notice
03/03/2018 18:53
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