Journal
HUMAN MOLECULAR GENETICS
Volume 22, Issue 16, Pages 3239-3249Publisher
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddt178
Keywords
-
Funding
- LCC
- ANR
- INCa
- INSERM
- Ligue Nationale contre le Cancer (Equipe Labellisee La Ligue)
- ARC
- INCa/Canceropole Ile de France
- European Research Council (PIDIMMUN grant) [249816]
- Fondation pour la Recherche Medicale (FRM)
- La Ligue contre le cancer
- Institut Imagine
- European Research Council (ERC) [249816] Funding Source: European Research Council (ERC)
Ask authors/readers for more resources
HoyeraalHreidarsson syndrome (HHS), a severe variant of dyskeratosis congenita (DC), is characterized by early onset bone marrow failure, immunodeficiency and developmental defects. Several factors involved in telomere length maintenance and/or protection are defective in HHS/DC, underlining the relationship between telomere dysfunction and these diseases. By combining whole-genome linkage analysis and exome sequencing, we identified compound heterozygous RTEL1 (regulator of telomere elongation helicase 1) mutations in three patients with HHS from two unrelated families. RTEL1 is a DNA helicase that participates in DNA replication, DNA repair and telomere integrity. We show that, in addition to short telomeres, RTEL1-deficient cells from patients exhibit hallmarks of genome instability, including spontaneous DNA damage, anaphase bridges and telomeric aberrations. Collectively, these results identify RTEL1 as a novel HHS-causing gene and highlight its role as a genomic caretaker in humans.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available