ArticleBlood2013
A homozygous telomerase T-motif variant resulting in markedly reduced repeat addition processivity in siblings with Hoyeraal Hreidarsson syndrome.
Article in Blood, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- Telomerase mutations in smokers with severe emphysema.The Journal of clinical investigation · 2015Trial
- Structures of human telomerase with BIBR1532 reveal novel mechanism of inhibition.Nature chemical biology · 2026Article
- Clonal Signatures of Telomere Biology Disorders.Current hematologic malignancy reports · 2026Review
- Dyskeratosis Congenita: Clinical Phenotype and Genetic Features in a Sibling Pair.Clinical, cosmetic and investigational dermatology · 2026Article
- Hematological complications in solid organ transplant recipients with telomere biology disorders: a narrative review.Frontiers in immunology · 2025Review
- Clinical mutations in the TERT and TERC genes coding for telomerase components induced oxidative stress, DNA damage at telomeres and cell apoptosis besides decreased telomerase activity.Human molecular genetics · 2024Article
- Giardia telomeres and telomerase.Parasitology research · 2024Review
- Adaptive and Maladaptive Clonal Hematopoiesis in Telomere Biology Disorders.Current hematologic malignancy reports · 2024Review
- Telomeres: Dysfunction, Maintenance, Aging and Cancer.Aging and disease · 2023Review
- Pot1b -/- tumors activate G-quadruplex-induced DNA damage to promote telomere hyper-elongation.Nucleic acids research · 2023Article
- Functional interaction between compound heterozygous TERT mutations causes severe telomere biology disorder.Blood advances · 2022Article
- Genetic and Epigenetic Inheritance at Telomeres.Epigenomes · 2022Review
- From incomplete penetrance with normal telomere length to severe disease and telomere shortening in a family with monoallelic and biallelic PARN pathogenic variants.Human mutation · 2019Article
- Complications for a Hoyeraal-Hreidarsson Syndrome Patient with a GermlineInternational journal of molecular sciences · 2019Article
- Telomere DNA G-quadruplex folding within actively extending human telomerase.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- A single nucleotide incorporation step limits human telomerase repeat addition activity.The EMBO journal · 2018Article
- Article
- Endogenous Telomerase Reverse Transcriptase N-Terminal Tagging Affects Human Telomerase Function at Telomeres In Vivo.Molecular and cellular biology · 2017Article
- Telomere biology and telomerase mutations in cirrhotic patients with hepatocellular carcinoma.PloS one · 2017Article
- The molecular genetics of the telomere biology disorders.RNA biology · 2016Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Hoyeraal Hreidarsson syndrome (HHS) is a form of dyskeratosis congenita (DC) characterized by bone marrow failure, intrauterine growth retardation, developmental delay, microcephaly, cerebellar hypoplasia, immunodeficiency, and extremely short telomeres. As with DC, mutations in genes encoding factors required for telomere maintenance, such as telomerase reverse transcriptase (TERT), have been found in patients with HHS. We describe 2 sibling HHS cases caused by a homozygous mutation (p.T567M) within the TERT T motif. This mutation resulted in a marked reduction in the capacity of telomerase to processively synthesize telomeric repeats, indicating a role for the T motif in this unique aspect of telomerase function. We support this finding by demonstrating defective processivity in the previously reported p.K570N T-motif mutation. The consanguineous, heterozygous p.T567M parents exhibited telomere lengths around the first percentile and no evidence of a DC phenotype. Although heterozygous processivity defects have been associated with familial, adult-onset pulmonary fibrosis, these cases demonstrate the severe clinical and functional impact of biallelic processivity mutations. Thus, despite retaining the capacity to add short stretches of telomeric repeats onto the shortest telomeres, sole expression of telomerase processivity mutants can lead to a profound failure of telomere maintenance and early-onset multisystem disease.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.