PuSH - Publikationsserver des Helmholtz Zentrums München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Kremer, L.S. ; Bader, D.M.* ; Mertes, C.* ; Kopajtich, R. ; Pichler, G.* ; Iuso, A. ; Haack, T.B. ; Graf, E. ; Schwarzmayr, T. ; Terrile, C. ; Konarikova, E. ; Repp, B. ; Kastenmüller, G. ; Adamski, J. ; Lichtner, P. ; Leonhardt, C.* ; Funalot, B.* ; Donati, A.* ; Tiranti, V.* ; Lombes, A.* ; Jardel, C.* ; Gläser, D.* ; Taylor, R.W.* ; Ghezzi, D.* ; Mayr, J.A.* ; Rötig, A.* ; Freisinger, P.* ; Distelmaier, F.* ; Strom, T.M. ; Meitinger, T. ; Gagneur, J.* ; Prokisch, H.

Genetic diagnosis of Mendelian disorders via RNA sequencing.

Nat. Commun. 8:15824 (2017)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Across a variety of Mendelian disorders, ∼50-75% of patients do not receive a genetic diagnosis by exome sequencing indicating disease-causing variants in non-coding regions. Although genome sequencing in principle reveals all genetic variants, their sizeable number and poorer annotation make prioritization challenging. Here, we demonstrate the power of transcriptome sequencing to molecularly diagnose 10% (5 of 48) of mitochondriopathy patients and identify candidate genes for the remainder. We find a median of one aberrantly expressed gene, five aberrant splicing events and six mono-allelically expressed rare variants in patient-derived fibroblasts and establish disease-causing roles for each kind. Private exons often arise from cryptic splice sites providing an important clue for variant prioritization. One such event is found in the complex I assembly factor TIMMDC1 establishing a novel disease-associated gene. In conclusion, our study expands the diagnostic tools for detecting non-exonic variants and provides examples of intronic loss-of-function variants with pathological relevance.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
12.124
2.995
224
289
Tags
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern

Zusatzinfos bearbeiten
Eigene Tags bearbeiten
Privat
Eigene Anmerkung bearbeiten
Privat
Auf Publikationslisten für
Homepage nicht anzeigen
Als besondere Publikation
markieren
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Random Monoallelic Expression; Perrault Syndrome; Complex I; Mutations; Tool; Disease; Snp; Mitochondria; Association; Deficiency
Sprache englisch
Veröffentlichungsjahr 2017
HGF-Berichtsjahr 2017
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 8, Heft: , Seiten: , Artikelnummer: 15824 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Human Genetics (IHG)
Institute of Bioinformatics and Systems Biology (IBIS)
Molekulare Endokrinologie und Metabolismus (MEM)
POF Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
30505 - New Technologies for Biomedical Discoveries
30201 - Metabolic Health
Forschungsfeld(er) Genetics and Epidemiology
Enabling and Novel Technologies
PSP-Element(e) G-500700-001
G-503700-001
G-505600-003
PubMed ID 28604674
DOI 10.1038/ncomms15824
WOS ID WOS:000403069900001
Scopus ID 85020697287
Erfassungsdatum 2017-07-14
[➜Korrektur melden]