Clinical and Molecular Characterization of Fanconi Anemia Patients in Turkey.

Autor:	Toksoy G; Department of Medical Genetics, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey., Uludağ Alkaya D; Department of Pediatric Genetics, Istanbul University-Cerrahpaşa, Medical School, Istanbul, Turkey., Bagirova G; Department of Medical Genetics, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey., Avcı Ş; Department of Medical Genetics, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.; Medical Genetics Department, Koç University School of Medicine, Istanbul, Turkey., Aghayev A; Department of Medical Genetics, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey., Günes N; Department of Pediatric Genetics, Istanbul University-Cerrahpaşa, Medical School, Istanbul, Turkey., Altunoğlu U; Department of Medical Genetics, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.; Medical Genetics Department, Koç University School of Medicine, Istanbul, Turkey., Alanay Y; Department of Pediatrics, Pediatric Genetics Unit, Acibadem Mehmet Ali Aydinlar University School of Medicine, Istanbul, Turkey., Başaran S; Department of Medical Genetics, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey., Berkay EG; Department of Medical Genetics, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey., Karaman B; Department of Medical Genetics, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.; Pediatric Basic Sciences, Child Health Institute, Istanbul University, Istanbul, Turkey., Celkan TT; Department of Pediatric Hematology-Oncology, Istanbul University-Cerrahpaşa, Medical School, Istanbul, Turkey., Apak H; Department of Pediatric Hematology-Oncology, Istanbul University-Cerrahpaşa, Medical School, Istanbul, Turkey., Kayserili H; Medical Genetics Department, Koç University School of Medicine, Istanbul, Turkey., Tüysüz B; Department of Pediatric Genetics, Istanbul University-Cerrahpaşa, Medical School, Istanbul, Turkey., Uyguner ZO; Department of Medical Genetics, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
Jazyk:	angličtina
Zdroj:	Molecular syndromology [Mol Syndromol] 2020 Nov; Vol. 11 (4), pp. 183-196. Date of Electronic Publication: 2020 Sep 23.
DOI:	10.1159/000509838
Abstrakt:	Fanconi anemia (FA) is a rare multigenic chromosomal instability syndrome that predisposes patients to life-threatening bone marrow failure, congenital malformations, and cancer. Functional loss of interstrand cross-link (ICL) DNA repair system is held responsible, though the mechanism is not yet fully understood. The clinical and molecular findings of 20 distinct FA cases, ages ranging from perinatal stage to 32 years, are presented here. Pathogenic variants in FANCA were found responsible in 75%, FANCC, FANCE, FANCJ / BRIP1, FANCL in 5%, and FANCD1 / BRCA2 and FANCN / PALB2 in 2.5% of the subjects. Altogether, 25 different variants in 7 different FA genes, including 10 novel mutations in FANCA, FANCN / PALB2, FANCE, and FANCJ / BRIP1, were disclosed. Two compound heterozygous germline cases were mosaic for one allele, revealing that the incidence of reverse mutations may not be uncommon in FA. Another case with de novo FANCD1/BRCA2 and paternally inherited FANCN/PALB2 pathogenic alleles at first glance suggested a digenic inheritance, because the presence of a second pathogenic variant in the unexamined regions of FANCD1/BRCA2 and FANCN/PALB2 were exluded by sequencing and deletion/duplication analysis. A better understanding of the complexity of the FA genotype may provide further access to undiscovered ICL components and apparently dispensable cellular pathways where FA proteins may play important roles. Competing Interests: The authors have no conflicts of interest to declare. (Copyright © 2020 by S. Karger AG, Basel.)
Databáze:	MEDLINE
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