Detection of a novel gross deletion in the UNC13D gene ends the diagnostic odyssey for a family with familial hemophagocytic lymphohistiocytosis 3

Abstract

Abstract Background: Familial hemophagocytic lymphohistiocytosis (FHL) is an immunological disorder characterized by overactivation of macrophages and T lymphocytes. This autosomal recessive condition has been characterized into multiple types depending on the genetic etiology. FHL type 3 is associated with bi-allelic pathogenic variants in the UNC13D gene. Case presentation: We present a 12-year diagnostic odyssey for a family with FHL that signifies the advances of FHL genetic testing in a diagnostic genetics laboratory with expertise in heritable immunodeficiencies. We describe the first case of a large UNC13D gross deletion in transto a sequence variant in a family with FHL3, which may have been mediated by Alu elements within introns 12 and 25 of the UNC13D gene. Conclusions: This case highlights the importance of reevaluating past genetic testing for a patient and family as test technology evolves in order to end a diagnostic odyssey.