Trio RNA sequencing in a cohort of medically complex children.
Journal
American journal of human genetics
ISSN: 1537-6605
Titre abrégé: Am J Hum Genet
Pays: United States
ID NLM: 0370475
Informations de publication
Date de publication:
04 05 2023
04 05 2023
Historique:
received:
28
11
2022
accepted:
08
03
2023
medline:
8
5
2023
pubmed:
30
3
2023
entrez:
29
3
2023
Statut:
ppublish
Résumé
Genome sequencing (GS) is a powerful test for the diagnosis of rare genetic disorders. Although GS can enumerate most non-coding variation, determining which non-coding variants are disease-causing is challenging. RNA sequencing (RNA-seq) has emerged as an important tool to help address this issue, but its diagnostic utility remains understudied, and the added value of a trio design is unknown. We performed GS plus RNA-seq from blood using an automated clinical-grade high-throughput platform on 97 individuals from 39 families where the proband was a child with unexplained medical complexity. RNA-seq was an effective adjunct test when paired with GS. It enabled clarification of putative splice variants in three families, but it did not reveal variants not already identified by GS analysis. Trio RNA-seq decreased the number of candidates requiring manual review when filtering for de novo dominant disease-causing variants, allowing for the exclusion of 16% of gene-expression outliers and 27% of allele-specific-expression outliers. However, clear diagnostic benefit from the trio design was not observed. Blood-based RNA-seq can facilitate genome analysis in children with suspected undiagnosed genetic disease. In contrast to DNA sequencing, the clinical advantages of a trio RNA-seq design may be more limited.
Identifiants
pubmed: 36990084
pii: S0002-9297(23)00090-3
doi: 10.1016/j.ajhg.2023.03.006
pmc: PMC10183368
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
895-900Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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