The causes of Fanconi anemia in South Asia and the Middle East: A case series and review of the literature.

Autor: Thompson AS; Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA., Saba N; Institute of Biomedical and Genetic Engineering, Islamabad, Pakistan., McReynolds LJ; Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA., Munir S; Institute of Biomedical and Genetic Engineering, Islamabad, Pakistan., Ahmed P; Quaid-i-Azam International Hospital, Islamabad, Pakistan., Sajjad S; Institute of Biomedical and Genetic Engineering, Islamabad, Pakistan., Jones K; Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD, 20850, USA., Yeager M; Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD, 20850, USA., Donovan FX; Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA., Chandrasekharappa SC; Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA., Alter BP; Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA., Savage SA; Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA., Rehman S; Institute of Biomedical and Genetic Engineering, Islamabad, Pakistan.
Jazyk: angličtina
Zdroj: Molecular genetics & genomic medicine [Mol Genet Genomic Med] 2021 Jul; Vol. 9 (7), pp. e1693. Date of Electronic Publication: 2021 May 07.
DOI: 10.1002/mgg3.1693
Abstrakt: Background: Fanconi anemia (FA) is an inherited bone marrow failure syndrome associated with characteristic dysmorphology primarily caused by biallelic pathogenic germline variants in any of 22 different DNA repair genes. There are limited data on the specific molecular causes of FA in different ethnic groups.
Methods: We performed exome sequencing and copy number variant analyses on 19 patients with FA from 17 families undergoing hematopoietic cell transplantation evaluation in Pakistan. The scientific literature was reviewed, and we curated germline variants reported in patients with FA from South Asia and the Middle East.
Results: The genetic causes of FA were identified in 14 of the 17 families: seven FANCA, two FANCC, one FANCF, two FANCG, and two FANCL. Homozygous and compound heterozygous variants were present in 12 and two families, respectively. Nine families carried variants previously reported as pathogenic, including two families with the South Asian FANCL founder variant. We also identified five novel likely deleterious variants in FANCA, FANCF, and FANCG in affected patients.
Conclusions: Our study supports the importance of determining the genomic landscape of FA in diverse populations, in order to improve understanding of FA etiology and assist in the counseling of families.
(© 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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