Clinical Severity Correlates with in VitroResidual Function of FANCBMissense Variants

Fanconi anemia (FA) is the most common inherited bone marrow failure syndrome, characterized by congenital anomalies, bone marrow failure and cancer predisposition. FA patients with mutations in FANCBexhibit X-linked inheritance pattern. FANCBpatients have been frequently associated with a severe phenotype, resembling VACTERL association with hydrocephalus, although heterogeneity in these patients still exists and is not well understood. To determine the underlying pathogenesis of clinical heterogeneity, we investigated phenotype-genotype correlations in 19 patients from 16 families with FANCBpathogenic variants. We also investigated functional properties of five FANCBmissense variants to determine their possible contribution to clinical manifestations.