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Article Dans Une Revue Human Molecular Genetics Année : 2013

Human RTEL1 deficiency causes Hoyeraal- Hreidarsson syndrome with short telomeres and genome instability

Patrick Revy

Résumé

Hoyeraal-Hreidarsson syndrome (HHS), a severe variant of dyskeratosis congenita (DC), is characterized by early onset bone marrowfailure, immunodeficiency and developmental defects. Several factors involved in telomere length maintenance and/or protection are defective in HHS/DC, underlining the relationship between telomeredysfunctionandthese diseases.Bycombining whole-genomelinkage analysisandexomesequencing,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.

Dates et versions

hal-00858583 , version 1 (05-09-2013)

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Citer

Tangui Leguen, Laurent Jullien, Fabien Touzot, Michael Schertzer, Laetitia Gaillard, et al.. Human RTEL1 deficiency causes Hoyeraal- Hreidarsson syndrome with short telomeres and genome instability. Human Molecular Genetics, 2013, 22 (16), pp.3239-3249. ⟨10.1093/hmg/ddt178⟩. ⟨hal-00858583⟩
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