A c.544_618del75bp mutation in the splicing factor gene PRPF31 is involved in non-syndromic retinitis pigmentosa by reducing the level of mRNA expression.
PRPF31
mRNA expression
retinitis pigmentosa
variation
Journal
Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)
ISSN: 1475-1313
Titre abrégé: Ophthalmic Physiol Opt
Pays: England
ID NLM: 8208839
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
28
09
2019
accepted:
02
01
2020
pubmed:
8
2
2020
medline:
22
7
2021
entrez:
8
2
2020
Statut:
ppublish
Résumé
A previous study reported a novel c.544_618del75bp mutation in exon 7 of the PRPF31 gene in a Chinese family with autosomal dominant retinal pigmentosa (ADRP). However, the selected pedigree was a small part of the whole family and the function of the c.544_618del75bp mutation was not explored deeply. The aim of the present study was to validate the previous results and explore the functional significance of the c.544_618del75bp mutation. We extended the size of the ADRP pedigree and sequenced DNA and cDNA of the PRPF31 gene for all members of the family and 100 healthy controls. Real-time quantitative polymerase chain reaction (PCR) analysis was performed on the cDNA of patients in the family and cell culture, plasmids transfection and western blot analysis were done to evaluate the functional effect of the mutation in vitro. Sanger sequencing showed that the mutation was present in all patients and absent in all normal individuals, except for participant III-9. Bioinformatics analysis revealed that the c.544_618del75bp mutation caused a 25 amino acid deletion in the PRPF31 protein. In addition, the mRNA expression assay revealed that the mRNA expression level of the PRPF31 and RP9 genes were significantly lower in RP patients than controls (p < 0.05). Finally, the in vitro transfection assay demonstrated that the mRNA expression level of the mutant transfection group was significantly lower than the wild-type transfection group (p < 0.05). Our study suggested that the c.544_618del75bp mutation in the PRPF31 gene was a causative mutation in this ADRP family and affected the expression of RP9 gene by influencing the formation of U4/U6-U5 tri-snRNP, eventually leading to the occurrence of RP.
Substances chimiques
Eye Proteins
0
PRPF31 protein, human
0
RNA, Messenger
0
DNA
9007-49-2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
289-299Informations de copyright
© 2020 The Authors Ophthalmic & Physiological Optics © 2020 The College of Optometrists.
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