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Splicing mutations in inherited retinal diseases.
Prog Retin Eye Res. 2020 Jun 15 [Online ahead of print]PR

Abstract

Mutations which induce aberrant transcript splicing represent a distinct class of disease-causing genetic variants in retinal disease genes. Such mutations may either weaken or erase regular splice sites or create novel splice sites which alter exon recognition. While mutations affecting the canonical GU-AG dinucleotides at the splice donor and splice acceptor site are highly predictive to cause a splicing defect, other variants in the vicinity of the canonical splice sites or those affecting additional cis-acting regulatory sequences within exons or introns are much more difficult to assess or even to recognize and require additional experimental validation. Splicing mutations are unique in that the actual outcome for the transcript (e.g. exon skipping, pseudoexon inclusion, intron retention) and the encoded protein can be quite different depending on the individual mutation. In this article, we present an overview on the current knowledge about and impact of splicing mutations in inherited retinal diseases. We introduce the most common sub-classes of splicing mutations including examples from our own work and others and discuss current strategies for the identification and validation of splicing mutations, as well as therapeutic approaches, open questions, and future perspectives in this field of research.

Authors+Show Affiliations

Molecular Genetics Laboratory, Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Germany.Molecular Genetics Laboratory, Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Germany.Molecular Genetics Laboratory, Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Germany. Electronic address: wissinger@uni-tuebingen.de.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

32553897

Citation

Weisschuh, Nicole, et al. "Splicing Mutations in Inherited Retinal Diseases." Progress in Retinal and Eye Research, 2020, p. 100874.
Weisschuh N, Buena-Atienza E, Wissinger B. Splicing mutations in inherited retinal diseases. Prog Retin Eye Res. 2020.
Weisschuh, N., Buena-Atienza, E., & Wissinger, B. (2020). Splicing mutations in inherited retinal diseases. Progress in Retinal and Eye Research, 100874. https://doi.org/10.1016/j.preteyeres.2020.100874
Weisschuh N, Buena-Atienza E, Wissinger B. Splicing Mutations in Inherited Retinal Diseases. Prog Retin Eye Res. 2020 Jun 15;100874. PubMed PMID: 32553897.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Splicing mutations in inherited retinal diseases. AU - Weisschuh,Nicole, AU - Buena-Atienza,Elena, AU - Wissinger,Bernd, Y1 - 2020/06/15/ PY - 2019/08/02/received PY - 2020/05/30/revised PY - 2020/05/31/accepted PY - 2020/6/20/pubmed PY - 2020/6/20/medline PY - 2020/6/20/entrez KW - Cryptic splice sites KW - Deep-intronic mutations KW - Inherited retinal disease KW - Splicing correction therapies KW - Splicing mutations SP - 100874 EP - 100874 JF - Progress in retinal and eye research JO - Prog Retin Eye Res N2 - Mutations which induce aberrant transcript splicing represent a distinct class of disease-causing genetic variants in retinal disease genes. Such mutations may either weaken or erase regular splice sites or create novel splice sites which alter exon recognition. While mutations affecting the canonical GU-AG dinucleotides at the splice donor and splice acceptor site are highly predictive to cause a splicing defect, other variants in the vicinity of the canonical splice sites or those affecting additional cis-acting regulatory sequences within exons or introns are much more difficult to assess or even to recognize and require additional experimental validation. Splicing mutations are unique in that the actual outcome for the transcript (e.g. exon skipping, pseudoexon inclusion, intron retention) and the encoded protein can be quite different depending on the individual mutation. In this article, we present an overview on the current knowledge about and impact of splicing mutations in inherited retinal diseases. We introduce the most common sub-classes of splicing mutations including examples from our own work and others and discuss current strategies for the identification and validation of splicing mutations, as well as therapeutic approaches, open questions, and future perspectives in this field of research. SN - 1873-1635 UR - https://www.unboundmedicine.com/medline/citation/32553897/Splicing_mutations_in_inherited_retinal_diseases L2 - https://linkinghub.elsevier.com/retrieve/pii/S1350-9462(20)30046-X DB - PRIME DP - Unbound Medicine ER -
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