Escher, Pascal; Passarin, Olga; Munier, Francis L; Tran, Viet H; Vaclavik, Veronika (2018). Variability in clinical phenotypes of PRPF8-linked autosomal dominant retinitis pigmentosa correlates with differential PRPF8/SNRNP200 interactions. Ophthalmic genetics, 39(1), pp. 80-86. Taylor & Francis 10.1080/13816810.2017.1393825
Full text not available from this repository.PURPOSE
To expand the genotype/phenotype correlations in patients with autosomal dominant retinitis pigmentosa (adRP) harboring PRPF8 variants.
MATERIALS AND METHODS
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.
RESULTS
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.
CONCLUSIONS
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.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Ophthalmology 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Augenklinik > Forschungsgruppe Augenheilkunde |
UniBE Contributor: |
Escher, Pascal |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1381-6810 |
Publisher: |
Taylor & Francis |
Language: |
English |
Submitter: |
Pascal Escher |
Date Deposited: |
01 Mar 2018 11:30 |
Last Modified: |
05 Dec 2022 15:09 |
Publisher DOI: |
10.1080/13816810.2017.1393825 |
PubMed ID: |
29087248 |
Uncontrolled Keywords: |
BRR2 PRPF8 SNRNP200 genotype/phenotype correlation retinitis pigmentosa spliceosome |
URI: |
https://boris.unibe.ch/id/eprint/110028 |
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