The evolving genetic landscape of telomere biology disorder dyskeratosis congenita
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F24%3A10484210" target="_blank" >RIV/00064165:_____/24:10484210 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11110/24:10484210
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=VSz5xUrXk~" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=VSz5xUrXk~</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s44321-024-00118-x" target="_blank" >10.1038/s44321-024-00118-x</a>
Alternative languages
Result language
angličtina
Original language name
The evolving genetic landscape of telomere biology disorder dyskeratosis congenita
Original language description
Dyskeratosis congenita (DC) is a rare inherited bone marrow failure syndrome, caused by genetic mutations that principally affect telomere biology. Approximately 35% of cases remain uncharacterised at the genetic level. To explore the genetic landscape, we conducted genetic studies on a large collection of clinically diagnosed cases of DC as well as cases exhibiting features resembling DC, referred to as 'DC-like' (DCL). This led us to identify several novel pathogenic variants within known genetic loci and in the novel X-linked gene, POLA1. In addition, we have also identified several novel variants in POT1 and ZCCHC8 in multiple cases from different families expanding the allelic series of DC and DCL phenotypes. Functional characterisation of novel POLA1 and POT1 variants, revealed pathogenic effects on protein-protein interactions with primase, CTC1-STN1-TEN1 (CST) and shelterin subunit complexes, that are critical for telomere maintenance. ZCCHC8 variants demonstrated ZCCHC8 deficiency and signs of pervasive transcription, triggering inflammation in patients' blood. In conclusion, our studies expand the current genetic architecture and broaden our understanding of disease mechanisms underlying DC and DCL disorders.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30101 - Human genetics
Result continuities
Project
—
Continuities
V - Vyzkumna aktivita podporovana z jinych verejnych zdroju
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
EMBO Molecular Medicine
ISSN
1757-4676
e-ISSN
1757-4684
Volume of the periodical
16
Issue of the periodical within the volume
10
Country of publishing house
GB - UNITED KINGDOM
Number of pages
23
Pages from-to
2560-2582
UT code for WoS article
001300659600001
EID of the result in the Scopus database
2-s2.0-85202491481