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Splicing in the diagnosis of rare disease: advances and challenges

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
1664-8021
689892
Lord, Jenny
e1909780-36cd-4705-b21e-4580038d4ec6
Baralle, Diana
faac16e5-7928-4801-9811-8b3a9ea4bb91
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, [689892]. (doi:10.3389/fgene.2021.689892).

Record type: Article

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.

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Lord_Baralle_Frontiers_review_accepted - Accepted Manuscript
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More information

Accepted/In Press date: 7 June 2021
Published date: 1 July 2021
Additional Information: Funding The Baralle Laboratory was supported by NIHR Research Professorship to DB (RP-2016-07-011).
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
ORCID for Jenny Lord: ORCID iD orcid.org/0000-0002-0539-9343
ORCID for Diana Baralle: ORCID iD orcid.org/0000-0003-3217-4833

Catalogue record

Date deposited: 21 Jun 2021 16:31
Last modified: 26 Nov 2021 03:17

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Contributors

Author: Jenny Lord ORCID iD
Author: Diana Baralle ORCID iD

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