biostudies-literatureYepez VABundesministerium für Bildung und ForschungInstituto de Salud Carlos IIIDeutsche ForschungsgemeinschaftDeutsches Zentrum für Herz-KreislaufforschungHelmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH)Medical Research CouncilAgency for Medical Research and DevelopmentNational Institute for Health Research (NIHR)Wellcome Trust Centre for Mitochondrial ResearchWellcome TrustLundbeck Foundation38https://www.ebi.ac.uk/biostudies/studies/S-EPMC8981716biostudies-literatureUnknown14(1)<h4>Background</h4>Lack of functional evidence hampers variant interpretation, leaving a large proportion of individuals with a suspected Mendelian disorder without genetic diagnosis after whole genome or whole exome sequencing (WES). Research studies advocate to further sequence transcriptomes to directly and systematically probe gene expression defects. However, collection of additional biopsies and establishment of lab workflows, analytical pipelines, and defined concepts in clinical interpretation of aberrant gene expression are still needed for adopting RNA sequencing (RNA-seq) in routine diagnostics.<h4>Methods</h4>We implemented an automated RNA-seq protocol and a computational workflow with which we analyzed skin fibroblasts of 303 individuals with a suspected mitochondrial diseaseGenome medicineClinical implementation of RNA sequencing for Mendelian disease diagnostics.PMC8981716PI16/01048R263-2017-438401KU2016A01IS18053FMR/S005021/1JP20ek0109468PDF-2018-11-ST2-021203105/Z/16/Z01GM1113CTerrile CFang FMuller MFVan Coster RProkisch HHempel MKishita YBeblo SMurayama KMeitinger TSchwarzmayr TOhtake AStrom TMXu MHayflick SJStaufner CNadel AFreisinger PWagner MTort FPiekutowska-Abramczuk DBan RYepez VARibes AKlopstock THaberle JWortmann SBSmet JGagneur JBlessing HMayr JARotig AItkis YSVanlander AGhezzi DAlston CLOkazaki YCiara ELamperti CSmith NHMertes CMunoz-Pujol GStenton SLDistelmaier FGusic MKrylova TDMosegaard SBerutti RKopajtich RTaylor RWMakowski CLenz DProcopio EfalseClinical implementation of RNA sequencing for Mendelian disease diagnostics.<h4>Background</h4>Lack of functional evidence hampers variant interpretation, leaving a large proportion of individuals with a suspected Mendelian disorder without genetic diagnosis after whole genome or whole exome sequencing (WES). Research studies advocate to further sequence transcriptomes to directly and systematically probe gene expression defects. However, collection of additional biopsies and establishment of lab workflows, analytical pipelines, and defined concepts in clinical interpretation of aberrant gene expression are still needed for adopting RNA sequencing (RNA-seq) in routine diagnostics.<h4>Methods</h4>We implemented an automated RNA-seq protocol and a computational workflow with which we analyzed skin fibroblasts of 303 individuals with a suspected mitochondrial disease2022-01-01T00:00:00Z2022 Apr2026-05-31T01:05:30.245Z2025-04-04T11:31:43.318ZS-EPMC89817163537932210.1186/s13073-022-01019-9