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

Nagaraj, CB; Brightman, DS; Rea, H; Wakefield, E; Harkavy, NVG; Dyer, L; Zhang, W

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

Nagaraj, CB Brightman, DS Rea, H Wakefield, E Harkavy, NVG Dyer, L Zhang, W

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Publisher:: BMC
Publication Type:: Journal Article
Citation:: BMC Pediatr, 2024, 24, (1), pp. 34
Issue Date:: 2024-01-11

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Field	Value	Language
dc.contributor.author	Nagaraj, CB
dc.contributor.author	Brightman, DS
dc.contributor.author	Rea, H
dc.contributor.author	Wakefield, E
dc.contributor.author	Harkavy, NVG
dc.contributor.author	Dyer, L
dc.contributor.author	Zhang, W
dc.date.accessioned	2025-05-05T22:48:26Z
dc.date.available	2023-12-26
dc.date.available	2025-05-05T22:48:26Z
dc.date.issued	2024-01-11
dc.identifier.citation	BMC Pediatr, 2024, 24, (1), pp. 34
dc.identifier.issn	1471-2431
dc.identifier.issn	1471-2431
dc.identifier.uri	http://hdl.handle.net/10453/187191
dc.description.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.
dc.format	Electronic
dc.language	eng
dc.publisher	BMC
dc.relation.ispartof	BMC Pediatr
dc.relation.isbasedon	10.1186/s12887-023-04510-3
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	1114 Paediatrics and Reproductive Medicine
dc.subject.classification	Pediatrics
dc.subject.classification	3213 Paediatrics
dc.subject.classification	4204 Midwifery
dc.subject.mesh	Humans
dc.subject.mesh	Alleles
dc.subject.mesh	Genetic Testing
dc.subject.mesh	Introns
dc.subject.mesh	Lymphohistiocytosis, Hemophagocytic
dc.subject.mesh	Membrane Proteins
dc.subject.mesh	Mutation
dc.subject.mesh	Child
dc.subject.mesh	Humans
dc.subject.mesh	Membrane Proteins
dc.subject.mesh	Mutation
dc.subject.mesh	Alleles
dc.subject.mesh	Introns
dc.subject.mesh	Child
dc.subject.mesh	Lymphohistiocytosis, Hemophagocytic
dc.subject.mesh	Genetic Testing
dc.subject.mesh	Humans
dc.subject.mesh	Alleles
dc.subject.mesh	Genetic Testing
dc.subject.mesh	Introns
dc.subject.mesh	Lymphohistiocytosis, Hemophagocytic
dc.subject.mesh	Membrane Proteins
dc.subject.mesh	Mutation
dc.subject.mesh	Child
dc.title	Detection of a novel gross deletion in the UNC13D gene ends the diagnostic odyssey for a family with familial hemophagocytic lymphohistiocytosis 3.
dc.type	Journal Article
utslib.citation.volume	24
utslib.location.activity	England
utslib.for	1114 Paediatrics and Reproductive Medicine
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Health
utslib.copyright.status	open_access	*
dc.rights.license	This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/
dc.date.updated	2025-05-05T22:48:21Z
pubs.issue	1
pubs.publication-status	Published online
pubs.volume	24
utslib.citation.issue	1

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.

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http://hdl.handle.net/10453/187191