Mutations in NR2E3 can cause dominant or recessive retinal degenerations in the same family.

Détails

Ressource 1Télécharger: BIB_07CD9A3E0C0E.P001.pdf (776.60 [Ko])
Etat: Public
Version: de l'auteur
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Télécharger: 19006237_Postprint.pdf (2212.75 [Ko])
Etat: Public
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ID Serval
serval:BIB_07CD9A3E0C0E
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Mutations in NR2E3 can cause dominant or recessive retinal degenerations in the same family.
Périodique
Human Mutation
Auteur(s)
Escher P., Gouras P., Roduit R., Tiab L., Bolay S., Delarive T., Chen S., Tsai C.C., Hayashi M., Zernant J., Merriam J.E., Mermod N., Allikmets R., Munier F.L., Schorderet D.F.
ISSN
1098-1004 ([electronic])
1059-7794 ([linking])
Statut éditorial
Publié
Date de publication
2009
Peer-reviewed
Oui
Volume
30
Numéro
3
Pages
342-351
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
NR2E3, a photoreceptor-specific nuclear receptor (PNR), represses cone-specific genes and activates several rod-specific genes. In humans, mutations in NR2E3 have been associated with the recessively-inherited enhanced short-wavelength sensitive S-cone syndrome (ESCS) and, recently, with autosomal dominant (ad) retinitis pigmentosa (RP) (adRP). In the present work, we describe two additional families affected by adRP that carry a heterozygous c.166G>A (p.G56R) mutation in the NR2E3 gene. Functional analysis determined the dominant negative activity of the p.G56R mutant protein as the molecular mechanism of adRP. Interestingly, in one pedigree, the most common causal variant for ESCS (p.R311Q) cosegregated with the adRP-linked p.G56R mutation, and the compound heterozygotes exhibited an ESCS-like phenotype, which in 1 of the 2 cases was strikingly "milder" than the patients carrying the p.G56R mutation alone. Impaired repression of cone-specific genes by the corepressors atrophin-1 (dentatorubral-pallidoluysian atrophy [DRPLA] gene product) and atrophin-2 (arginine-glutamic acid dipeptide repeat [RERE] protein) appeared to be a molecular mechanism mediating the beneficial effect of the p.R311Q mutation. Finally, the functional dominance of the p.R311Q variant to the p.G56R mutation is discussed.
Mots-clé
Adolescent, Adult, Aged, Amino Acid Sequence, Animals, Cell Line, Electrophoretic Mobility Shift Assay, Family Health, Female, Genes, Dominant, Genes, Recessive, Genotype, Humans, Male, Mice, Mice, Inbred C57BL, Molecular Sequence Data, Mutation, Orphan Nuclear Receptors, Pedigree, Protein Binding, Receptors, Cytoplasmic and Nuclear/genetics, Receptors, Cytoplasmic and Nuclear/metabolism, Retinal Degeneration/genetics, Retinal Degeneration/pathology, Retinitis Pigmentosa/genetics, Retinitis Pigmentosa/pathology, Sequence Homology, Amino Acid, Transcription Factors/genetics, Transcription Factors/metabolism, Young Adult
Pubmed
Web of science
Création de la notice
19/03/2009 11:36
Dernière modification de la notice
20/08/2019 12:30
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