PuSH - Publikationsserver des Helmholtz Zentrums München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Brunet, T. ; Berutti, R. ; Dill, V.* ; Hecker, J.S.* ; Choukair, D.* ; Andres, S.* ; Deschauer, M.* ; Diehl-Schmid, J.* ; Krenn, M.* ; Eckstein, G. ; Graf, E.* ; Gasser, T.* ; Strom, T.M.* ; Hoefele, J.* ; Götze, K.S.* ; Meitinger, T.* ; Wagner, M.

Clonal hematopoiesis as a pitfall in germline variant interpretation in the context of Mendelian disorders.

Hum. Mol. Genet. 31, 2386-2395 (2022)
Verlagsversion DOI PMC
Closed
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Clonal hematopoiesis due to somatic mutations in hematopoietic stem/progenitor cells is an age-related phenomenon and commonly observed when sequencing blood DNA in elderly individuals. Several genes that are implicated in clonal hematopoiesis are also associated with Mendelian disorders when mutated in the germline, potentially leading to variant misinterpretation. We performed a literature search to identify genes associated with age-related clonal hematopoiesis followed by an OMIM query to identify the subset of genes in which germline variants are associated with Mendelian disorders. We retrospectively screened for diagnostic cases in which the presence of age-related clonal hematopoiesis confounded exome sequencing data interpretation. We found 58 genes in which somatic mutations are implicated in clonal hematopoiesis while germline variants in the same genes are associated with Mendelian (mostly neurodevelopmental) disorders. Using five selected cases of individuals with suspected monogenic disorders, we illustrate how clonal hematopoiesis in either variant databases or exome sequencing datasets poses a pitfall, potentially leading to variant misclassification and erroneous conclusions regarding gene-disease associations.
Impact Factor
Scopus SNIP
Scopus
Cited By
Altmetric
5.121
0.000
2
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
Sprache englisch
Veröffentlichungsjahr 2022
HGF-Berichtsjahr 2022
ISSN (print) / ISBN 0964-6906
e-ISSN 1460-2083
Zeitschrift Human Molecular Genetics
Quellenangaben Band: 31, Heft: 14, Seiten: 2386-2395 Artikelnummer: , Supplement: ,
Verlag Oxford University Press
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Neurogenomics (ING)
POF Topic(s) 30205 - Bioengineering and Digital Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-503200-001
G-503292-001
DOI 10.1093/hmg/ddac034
WOS ID WOS:000770414000001
PubMed ID 35179199
Erfassungsdatum 2022-06-28
[➜Korrektur melden]