Unveiling a pathogenic FANCA gene variant in a Mexican family with Fanconi anemia through next‑generation sequencing

Abstract

Fanconi anemia (FA) is the most common hereditary bone marrow failure syndrome, with an incidence of 1 in 5,000,000. This disease is caused by an alteration in one of the 23 genes associated with the FA/BRCA DNA repair pathway, which is responsible for repairing interstrand bridges generated during homologous recombination. FA has been associated with a predisposition to other types of neoplasm. The current study aimed to present a pathogenic variant in FANCA observed in three Mexican siblings, as detected by next-generation sequencing (NGS). The results of an induced chromosomal breakage test showed chromosomal breaks and radial figures, which were compatible with FA, and a normal karyotype. NGS TruSight Hereditary Cancer Panel analysis resulted in the FANCA:c.3931_3932delAG variant being classified as pathogenic according to bioinformatics analysis. The present study reports a pathogenic variant in FANCA that was found in a Mexican family with FA, in which one of the siblings exhibited a suggestive mucosa-assisted lymphoid tissue lymphoma, which is an atypical presentation of neoplasia associated with FA.