| Autor: |
Marijana, Virijević, Irena, Marjanovic, Marina, Andjelkovic, Teodora, Karan-Djurasevic, Branka, Zukic, Jovana, Komazec, Ivana, Grubisa, Biljana, Stankovic, Andrija, Bogdanović, Sonja, Pavlovic |
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| Zdroj: |
Genetics & Applications; 2024 Special Issue, p42-42, 1p |
| Abstrakt: |
TERT gene, the most frequently mutated gene in patients with telomere biology disorders (telomeropathies), encode telomerase reverse transcriptase enzyme. Heterozygous variants in the TERT gene impair telomerase activity by haploinsufficiency and pathogenic variants are associated with bone marrow failure syndrome and acute myeloid leukemia predisposition. TERT variants show incomplete penetrance and can also be found in asymptomatic family members. Due to the rarity of the disease and the small number of clinical trials, telomeropathies are often unrecognized and misdiagnosed. To report a novel variant in TERT gene in familial hematopoetic disorder. Methodology: Next Generation Sequencing of DNA isolated from peripheral blood of a patient (older sister) with clinical diagnosis of aplastic anemia, using TruSight One MiSeq platform (Illumina®) and segregation sequencing analysis of patient’s mother and younger sister. We identified a novel missense heterozygous variant c.2605G>A p.(Asp869Asn) in TERT gene in a family of mother and two daughters. This variant results in replacement of aspartic amino acid on 869 position in TERT enzyme polypeptide chain by asparagine. It is located in highly conserved protein region and is very likely to disrupt the function of the enzyme. According to ACMG classification, detected variant is characterized as likely pathogenic, class 2. As patients with telomeropathies often have a history of macrocytosis and thrombocytopenia, often wrongly diagnosed as immune-mediated thrombocytopenia, myelodysplastic syndrome or aplastic anemia, our findings indicate that TERT rare variants pass under-recognized in these patients. For that reason, our findings point out the importance for routine deep genetics screening for TERT rare variants in patients with family history of different bone marrow failure syndromes. Which could identify clinically inapparent telomere biology disorder and improve outcomes through forehand diagnosis setting, genetic counseling and the precise therapy consideration. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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