Unraveling the pathogenesis of Hoyeraal-Hreidarsson syndrome, a complex telomere biology disorder

Galina Glousker, Fabien Touzot, Patrick Revy, Yehuda Tzfati, Sharon A. Savage*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

92 Scopus citations

Abstract

Hoyeraal-Hreidarsson (HH) syndrome is a multisystem genetic disorder characterized by very short telomeres and considered a clinically severe variant of dyskeratosis congenita. The main cause of mortality, usually in early childhood, is bone marrow failure. Mutations in several telomere biology genes have been reported to cause HH in about 60% of the HH patients, but the genetic defects in the rest of the patients are still unknown. Understanding the aetiology of HH and its diverse manifestations is challenging because of the complexity of telomere biology and the multiple telomeric and non-telomeric functions played by telomere-associated proteins in processes such as telomere replication, telomere protection, DNA damage response and ribosome and spliceosome assembly. Here we review the known clinical complications, molecular defects and germline mutations associated with HH, and elucidate possible mechanistic explanations and remaining questions in our understanding of the disease.

Original languageAmerican English
Pages (from-to)457-471
Number of pages15
JournalBritish Journal of Haematology
Volume170
Issue number4
DOIs
StatePublished - 1 Aug 2015

Bibliographical note

Publisher Copyright:
© 2015 John Wiley & Sons Ltd.

Keywords

  • Cerebellar hypoplasia
  • Dyskeratosis congenita
  • Hoyeraal-Hreidarsson syndrome
  • Immunodeficiency
  • Telomere

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