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

被引:92
作者
Glousker, Galina [1 ]
Touzot, Fabien [2 ]
Revy, Patrick [2 ]
Tzfati, Yehuda [1 ]
Savage, Sharon A. [3 ]
机构
[1] Hebrew Univ Jerusalem, Dept Genet, Silberman Inst Life Sci, IL-91904 Jerusalem, Israel
[2] Paris Descartes Sorbonne Paris Cite Univ, INSERM, Lab Genome Dynam Immune Syst, UMR 1163, Paris, France
[3] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA
基金
欧洲研究理事会; 美国国家卫生研究院; 以色列科学基金会;
关键词
Hoyeraal-Hreidarsson syndrome; dyskeratosis congenita; telomere; immunodeficiency; cerebellar hypoplasia; LINKED DYSKERATOSIS-CONGENITA; BONE-MARROW FAILURE; SMALL NUCLEOLAR RNA; REVERSE-TRANSCRIPTASE; CEREBELLAR HYPOPLASIA; COMBINED IMMUNODEFICIENCY; PROGRESSIVE PANCYTOPENIA; GROWTH-RETARDATION; GERMLINE MUTATION; APLASTIC-ANEMIA;
D O I
10.1111/bjh.13442
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:457 / 471
页数:15
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