Comprehensive laboratory diagnosis of Fanconi anaemia: comparison of cellular and molecular analysis.

Autor:	Joshi G; Department of Haematology, Christian Medical College Vellore, Vellore, Tamil Nadu, India.; Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India., Arthur NBJ; Department of Haematology, Christian Medical College Vellore, Vellore, Tamil Nadu, India., Geetha TS; MedGenome Laboratories Pvt Ltd, Bangalore, India., Datari PVR; Department of Haematology, Christian Medical College Vellore, Vellore, Tamil Nadu, India., Modak K; Department of Haematology, Christian Medical College Vellore, Vellore, Tamil Nadu, India., Roy D; Department of Haematology, Christian Medical College Vellore, Vellore, Tamil Nadu, India.; Manipal Academy of Higher Education, Manipal, Karnataka, India., Chaudhury AD; Department of Haematology, Christian Medical College Vellore, Vellore, Tamil Nadu, India., Sundaraganesan P; Department of Haematology, Christian Medical College Vellore, Vellore, Tamil Nadu, India., Priyanka S; Department of Haematology, Christian Medical College Vellore, Vellore, Tamil Nadu, India., Na F; Department of Haematology, Christian Medical College Vellore, Vellore, Tamil Nadu, India., Ramprasad V; MedGenome Laboratories Pvt Ltd, Bangalore, India., Abraham A; Department of Haematology, Christian Medical College Vellore, Vellore, Tamil Nadu, India., Srivastava VM; Department of Cytogenetics, Christian Medical College Vellore, Vellore, Tamil Nadu, India., Srivastava A; Department of Haematology, Christian Medical College Vellore, Vellore, Tamil Nadu, India.; Center for Stem Cell Research, Vellore, Tamil Nadu, India., Kulkarni UP; Department of Haematology, Christian Medical College Vellore, Vellore, Tamil Nadu, India., George B; Department of Haematology, Christian Medical College Vellore, Vellore, Tamil Nadu, India., Velayudhan SR; Department of Haematology, Christian Medical College Vellore, Vellore, Tamil Nadu, India rvshaji@cmcvellore.ac.in.; Center for Stem Cell Research, Vellore, Tamil Nadu, India.
Jazyk:	angličtina
Zdroj:	Journal of medical genetics [J Med Genet] 2023 Aug; Vol. 60 (8), pp. 801-809. Date of Electronic Publication: 2023 Mar 09.
DOI:	10.1136/jmg-2022-108714
Abstrakt:	Background: Fanconi anaemia (FA) is a rare inherited bone marrow failure disease caused by germline pathogenic variants in any of the 22 genes involved in the FA-DNA interstrand crosslink (ICL) repair pathway. Accurate laboratory investigations are required for FA diagnosis for the clinical management of the patients. We performed chromosome breakage analysis (CBA), FANCD2 ubiquitination (FANCD2-Ub) analysis and exome sequencing of 142 Indian patients with FA and evaluated the efficiencies of these methods in FA diagnosis. Methods: We performed CBA and FANCD2-Ub analysis in the blood cells and fibroblasts of patients with FA. Exome sequencing with improved bioinformatics to detect the single number variants and CNV was carried out for all the patients. Functional validation of the variants with unknown significance was done by lentiviral complementation assay. Results: Our study showed that FANCD2-Ub analysis and CBA on peripheral blood cells could diagnose 97% and 91.5% of FA cases, respectively. Exome sequencing identified the FA genotypes consisting of 45 novel variants in 95.7% of the patients with FA. FANCA (60.2%), FANCL (19.8%) and FANCG (11.7%) were the most frequently mutated genes in the Indian population. A FANCL founder mutation c.1092G>A; p.K364=was identified at a very high frequency (~19%) in our patients. Conclusion: We performed a comprehensive analysis of the cellular and molecular tests for the accurate diagnosis of FA. A new algorithm for rapid and cost-effective molecular diagnosis for~90% of FA cases has been established. Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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