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

BMC Pediatr. 2024 Jan 11;24(1):34. doi: 10.1186/s12887-023-04510-3.

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 clinical genetic diagnostic laboratory setting. We describe the first case of a large UNC13D gross deletion in trans to a nonsense 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 re-evaluating past genetic testing for a patient and family as test technology evolves in order to end a diagnostic odyssey.

Keywords: Deletion; Diagnostic odyssey; Familial hemophagocytic lymphohistiocytosis type 3; UNC13D.

Publication types

  • Case Reports

MeSH terms

  • Alleles
  • Child
  • Genetic Testing
  • Humans
  • Introns
  • Lymphohistiocytosis, Hemophagocytic* / diagnosis
  • Lymphohistiocytosis, Hemophagocytic* / genetics
  • Membrane Proteins / genetics
  • Mutation

Substances

  • Membrane Proteins
  • UNC13D protein, human