Genotyping Fanconi Anemia Patients from Serbia Reveals Three Novel Fancd2 Variants
Аутори
Filipović Tričković, Jelena G.Mandušić, Vesna
Joksić, Ivana
Vujić, Dragana
Valenta-Šobot, Ana
Joksić, Gordana
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Fanconi anemia is rare inherited disease characterized by wide spectrum of congenital anomalies, progressive pancytopenia, and predisposition to hematological malignancies and solid tumors. Molecular genetic analysis of mutations in FANC genes is of a great importance for diagnosis confirmation, prenatal and carrier testing, as well as for prediction of chemotherapy outcome and disease complications. In this study we performed screening of frequently affected regions of FANCD2 gene for sequence variants in six unrelated FA-D2 patients in Serbia. This is the first molecular analysis of FANCD2 gene in Serbian FA-D2 patients. A total of 10 sequence variants were detected, one in homozygous, and nine in heterozygous state. Two variants were found within exons, and eight within introns, in deep intronic regions. In-silico analysis showed that among all detected variants one exon variant and three intron variants might have impact on splicing mechanism. Heterozygous variants found in intron ...3, c. 206-246delG; exon 26, c. 2396 C GT A and intron 28, c. 2715+573 C GT T were not previously reported. In-silico analysis revealed that among them, two (intron 3, c. 206-246 delG and exon 26, c. 2396 C GT A) could be novel disease-causing mutations. Many variants were found in more than one patient, including those unreported, indicating their possible ethnic association. Great number of variants in some patients suggests their non-random emergence in Fanconi anemia pathway.
Кључне речи:
deep intronic variants / Fanconi anemia / FANCD2 variants / splicing mechanismИзвор:
Genetika, 2017, 49, 2, 559-572Финансирање / пројекти:
- Радиосензитивност хуманог генома (RS-MESTD-Basic Research (BR or ON)-173046)
DOI: 10.2298/GENSR1702559T
ISSN: 0534-0012; 1820-6069
WoS: 000418533000015
Scopus: 2-s2.0-85033607868
Институција/група
VinčaTY - JOUR AU - Filipović Tričković, Jelena G. AU - Mandušić, Vesna AU - Joksić, Ivana AU - Vujić, Dragana AU - Valenta-Šobot, Ana AU - Joksić, Gordana PY - 2017 UR - https://vinar.vin.bg.ac.rs/handle/123456789/1882 AB - Fanconi anemia is rare inherited disease characterized by wide spectrum of congenital anomalies, progressive pancytopenia, and predisposition to hematological malignancies and solid tumors. Molecular genetic analysis of mutations in FANC genes is of a great importance for diagnosis confirmation, prenatal and carrier testing, as well as for prediction of chemotherapy outcome and disease complications. In this study we performed screening of frequently affected regions of FANCD2 gene for sequence variants in six unrelated FA-D2 patients in Serbia. This is the first molecular analysis of FANCD2 gene in Serbian FA-D2 patients. A total of 10 sequence variants were detected, one in homozygous, and nine in heterozygous state. Two variants were found within exons, and eight within introns, in deep intronic regions. In-silico analysis showed that among all detected variants one exon variant and three intron variants might have impact on splicing mechanism. Heterozygous variants found in intron 3, c. 206-246delG; exon 26, c. 2396 C GT A and intron 28, c. 2715+573 C GT T were not previously reported. In-silico analysis revealed that among them, two (intron 3, c. 206-246 delG and exon 26, c. 2396 C GT A) could be novel disease-causing mutations. Many variants were found in more than one patient, including those unreported, indicating their possible ethnic association. Great number of variants in some patients suggests their non-random emergence in Fanconi anemia pathway. T2 - Genetika T1 - Genotyping Fanconi Anemia Patients from Serbia Reveals Three Novel Fancd2 Variants VL - 49 IS - 2 SP - 559 EP - 572 DO - 10.2298/GENSR1702559T ER -
@article{ author = "Filipović Tričković, Jelena G. and Mandušić, Vesna and Joksić, Ivana and Vujić, Dragana and Valenta-Šobot, Ana and Joksić, Gordana", year = "2017", abstract = "Fanconi anemia is rare inherited disease characterized by wide spectrum of congenital anomalies, progressive pancytopenia, and predisposition to hematological malignancies and solid tumors. Molecular genetic analysis of mutations in FANC genes is of a great importance for diagnosis confirmation, prenatal and carrier testing, as well as for prediction of chemotherapy outcome and disease complications. In this study we performed screening of frequently affected regions of FANCD2 gene for sequence variants in six unrelated FA-D2 patients in Serbia. This is the first molecular analysis of FANCD2 gene in Serbian FA-D2 patients. A total of 10 sequence variants were detected, one in homozygous, and nine in heterozygous state. Two variants were found within exons, and eight within introns, in deep intronic regions. In-silico analysis showed that among all detected variants one exon variant and three intron variants might have impact on splicing mechanism. Heterozygous variants found in intron 3, c. 206-246delG; exon 26, c. 2396 C GT A and intron 28, c. 2715+573 C GT T were not previously reported. In-silico analysis revealed that among them, two (intron 3, c. 206-246 delG and exon 26, c. 2396 C GT A) could be novel disease-causing mutations. Many variants were found in more than one patient, including those unreported, indicating their possible ethnic association. Great number of variants in some patients suggests their non-random emergence in Fanconi anemia pathway.", journal = "Genetika", title = "Genotyping Fanconi Anemia Patients from Serbia Reveals Three Novel Fancd2 Variants", volume = "49", number = "2", pages = "559-572", doi = "10.2298/GENSR1702559T" }
Filipović Tričković, J. G., Mandušić, V., Joksić, I., Vujić, D., Valenta-Šobot, A.,& Joksić, G.. (2017). Genotyping Fanconi Anemia Patients from Serbia Reveals Three Novel Fancd2 Variants. in Genetika, 49(2), 559-572. https://doi.org/10.2298/GENSR1702559T
Filipović Tričković JG, Mandušić V, Joksić I, Vujić D, Valenta-Šobot A, Joksić G. Genotyping Fanconi Anemia Patients from Serbia Reveals Three Novel Fancd2 Variants. in Genetika. 2017;49(2):559-572. doi:10.2298/GENSR1702559T .
Filipović Tričković, Jelena G., Mandušić, Vesna, Joksić, Ivana, Vujić, Dragana, Valenta-Šobot, Ana, Joksić, Gordana, "Genotyping Fanconi Anemia Patients from Serbia Reveals Three Novel Fancd2 Variants" in Genetika, 49, no. 2 (2017):559-572, https://doi.org/10.2298/GENSR1702559T . .