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

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2024年1月11日

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Chinmayee B. Nagaraj,
Diana S. Brightman,
Hannah Rea,
Emily Wakefield,
Nina V. G. Harkavy,
Lisa Dyer,
Wenying Zhang

摘要

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.