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Impact of thrombocytopenia-associated c.-118C>T and c.-140C>G ANKRD26 5'UTR variants in three-generational pedigree
J. Trizuljak, P. Likavcová, K. Staňo Kozubík, Z. Vrzalová, J. Hynšt, T. Deissová, J. Štika, L. Radová, M. Prudková, J. Vaculová, I. Blaháková, P. Smejkal, J. Kamelander, Š. Pospíšilová, M. Doubek
Language English Country England, Great Britain
Document type Journal Article
NLK
Directory of Open Access Journals
from 2023
Taylor & Francis Open Access
from 2023-12-01
Medline Complete (EBSCOhost)
from 1999-01-01
ROAD: Directory of Open Access Scholarly Resources
from 1990
- MeSH
- 5' Untranslated Regions * MeSH
- Adult MeSH
- Genetic Predisposition to Disease MeSH
- Middle Aged MeSH
- Humans MeSH
- Intercellular Signaling Peptides and Proteins MeSH
- Pedigree * MeSH
- Thrombocytopenia * genetics MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Inherited thrombocytopenias (ITs) encompass a group of rare disorders characterized by diminished platelet count. Recent advancements have unveiled various forms of IT, with inherited thrombocytopenia 2 (THC2) emerging as a prevalent subtype associated with germline variants in the critical 5' untranslated region of the ANKRD26 gene. This region is crucial in regulating the gene expression of ANKRD26, particularly in megakaryocytes. THC2 is an autosomal dominant disorder presenting as mild-to-moderate thrombocytopenia with minimal symptoms, with an increased risk of myeloproliferative malignancies. In our study of a family with suspected IT, three affected individuals harbored the c.-118C>T ANKRD26 variant, while four healthy members carried the c.-140C>G ANKRD26 variant. We performed a functional analysis by studying platelet-specific ANKRD26 gene expression levels using quantitative real-time polymerase-chain reaction. Functional analysis of the c.-118C>T variant showed a significant increase in ANKRD26 expression in affected individuals, supporting its pathogenicity. On the contrary, carriers of the c.-140C>G variant exhibited normal platelet counts and no significant elevation in the ANKRD26 expression, indicating the likely benign nature of this variant. Our findings provide evidence confirming the pathogenicity of the c.-118C>T ANKRD26 variant in THC2 and suggest the likely benign nature of the c.-140C>G variant.
Department of Clinical Haematology and Haematooncology Hospital Havířov Havířov Czech Republic
Department of Clinical Haematology University Hospital Brno Masaryk University Brno Czech Republic
Department of Laboratory Methods Faculty of Medicine Masaryk University Brno Czech Republicand
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