Splicing in the diagnosis of rare disease: advances and challenges
Splicing in the diagnosis of rare disease: advances and challenges
Mutations which affect splicing are significant contributors to rare disease, but are frequently overlooked by diagnostic sequencing pipelines. Greater ascertainment of pathogenic splicing variants will increase diagnostic yields, ending the diagnostic odyssey for patients and families affected by rare disorders, and improving treatment and care strategies. Advances in sequencing technologies, predictive modeling, and understanding of the mechanisms of splicing in recent years pave the way for improved detection and interpretation of splice affecting variants, yet several limitations still prohibit their routine ascertainment in diagnostic testing. This review explores some of these advances in the context of clinical application and discusses challenges to be overcome before these variants are comprehensively and routinely recognized in diagnostics.
RNA, RNA-seq, diagnostics, rare disease, splicing
689892
Lord, Jenny
e1909780-36cd-4705-b21e-4580038d4ec6
Baralle, Diana
faac16e5-7928-4801-9811-8b3a9ea4bb91
1 July 2021
Lord, Jenny
e1909780-36cd-4705-b21e-4580038d4ec6
Baralle, Diana
faac16e5-7928-4801-9811-8b3a9ea4bb91
Lord, Jenny and Baralle, Diana
(2021)
Splicing in the diagnosis of rare disease: advances and challenges.
Frontiers in Genetics, 12, , [689892].
(doi:10.3389/fgene.2021.689892).
Abstract
Mutations which affect splicing are significant contributors to rare disease, but are frequently overlooked by diagnostic sequencing pipelines. Greater ascertainment of pathogenic splicing variants will increase diagnostic yields, ending the diagnostic odyssey for patients and families affected by rare disorders, and improving treatment and care strategies. Advances in sequencing technologies, predictive modeling, and understanding of the mechanisms of splicing in recent years pave the way for improved detection and interpretation of splice affecting variants, yet several limitations still prohibit their routine ascertainment in diagnostic testing. This review explores some of these advances in the context of clinical application and discusses challenges to be overcome before these variants are comprehensively and routinely recognized in diagnostics.
Text
Lord_Baralle_Frontiers_review_accepted
- Accepted Manuscript
More information
Accepted/In Press date: 7 June 2021
Published date: 1 July 2021
Additional Information:
Funding Information:
The Baralle Laboratory was supported by NIHR Research Professorship to DB (RP-2016-07-011).
Publisher Copyright:
© Copyright © 2021 Lord and Baralle.
Keywords:
RNA, RNA-seq, diagnostics, rare disease, splicing
Identifiers
Local EPrints ID: 449837
URI: http://eprints.soton.ac.uk/id/eprint/449837
ISSN: 1664-8021
PURE UUID: ddf4f845-de4a-4a14-aea4-d9575d369b7d
Catalogue record
Date deposited: 21 Jun 2021 16:31
Last modified: 17 Mar 2024 03:54
Export record
Altmetrics
Contributors
Author:
Jenny Lord
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics