Variability in clinical phenotypes of PRPF8-linked autosomal dominant retinitis pigmentosa correlates with differential PRPF8/SNRNP200 interactions.

Détails

ID Serval
serval:BIB_F655CBFD30FC
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Variability in clinical phenotypes of PRPF8-linked autosomal dominant retinitis pigmentosa correlates with differential PRPF8/SNRNP200 interactions.
Périodique
Ophthalmic genetics
Auteur(s)
Escher P., Passarin O., Munier F.L., Tran V.H., Vaclavik V.
ISSN
1744-5094 (Electronic)
ISSN-L
1381-6810
Statut éditorial
Publié
Date de publication
2018
Peer-reviewed
Oui
Volume
39
Numéro
1
Pages
80-86
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
To expand the genotype/phenotype correlations in patients with autosomal dominant retinitis pigmentosa (adRP) harboring PRPF8 variants.
Two patients, a father and his daughter, harboring a novel p.PRPF8-Glu2331* variant, underwent ophthalmic examination at 3-year-interval, including fundus photography, fundus autofluorescence, optical coherence tomography, and ISCEV standard full field ERGs. All reported disease-causing PRPF8 variants were collected and localized in the PRPF8 and PRPF8/SNRNP200 protein structures.
The p.PRPF8-Glu2331* variant results in a truncated PRPF8 protein lacking the last five C-terminal amino acids and caused in the two patients a severe clinical phenotype, with the macula being affected from the second decade on. All but two adRP-linked variants are located in the last exon 43 encoding the C-terminal tail of the C-terminal PRPF8 Jab1 domain. The p.PRPF8-Ser2118Phe and -Asn2280Lys variants encoded by exons 39 and 42, respectively, are located at the basis of the C-terminal tail.
Frame-shift mutations and nonconservative amino acid changes in PRPF8 typically cause severe clinical phenotypes. The conservative missense variant p.PRPF8-Arg2310Lys that is not altering the global charge of the C-terminal tail, and variants located at the basis of the C-terminal tail show milder clinical phenotypes, in accordance with functional data on PRPF8/SNRNP200 interactions in yeast.

Mots-clé
Adult, Amino Acid Sequence, DNA Mutational Analysis, Female, Fluorescein Angiography, Genes, Dominant, Genetic Association Studies, Humans, Male, Middle Aged, Molecular Sequence Data, Mutation, Missense, Pedigree, Phenotype, Protein Conformation, RNA-Binding Proteins/genetics, Retinitis Pigmentosa/diagnosis, Retinitis Pigmentosa/genetics, Ribonucleoproteins, Small Nuclear/genetics, Tomography, Optical Coherence, BRR2, PRPF8, SNRNP200, genotype/phenotype correlation, retinitis pigmentosa, spliceosome
Pubmed
Web of science
Création de la notice
09/11/2017 17:27
Dernière modification de la notice
20/08/2019 16:22
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