Whole exome sequencing identifies functional classes of gene mutations associated with bone marrow failure in pediatric Fanconi Anemia patients.

Fanconi anemia (FA) is an inherited bone marrow failure syndrome characterized by biallelic germline mutations in FA genes in the DNA damage repair pathway. Defective DNA damage repair leading to genomic instability suggests a role of acquired somatic mutations in disease progression to bone marrow failure (BMF). We hypothesize that the somatic mutational landscape of FA patients can predict the development of BMF, the most common cause of morbidity and mortality in this patient population. To identify somatic mutations associated with BMF in FA patients, we performed whole-exome sequencing (WES) of bone marrow samples from five pediatric patients with FA. This case series is the first to report the functional classes of somatic gene mutations associated with BMF in FA patients, which may aid in prognostication of disease severity and clinical outcomes.