Hypomorphic mutations in PRF1, MUNC13-4, and STXBP2 are associated with adult-onset familial HLH.
Published
Journal Article
Familial hemophagocytic lymphohistiocytosis (HLH) is a rare primary immunodeficiency disorder characterized by defects in cell-mediated cytotoxicity that results in fever, hepatosplenomegaly, and cytopenias. Familial HLH is well recognized in children but rarely diagnosed in adults. We conducted a retrospective review of genetic and immunologic test results in patients who developed HLH in adulthood. Included in our study were 1531 patients with a clinical diagnosis of HLH; 175 patients were 18 years or older. Missense and splice-site sequence variants in PRF1, MUNC13-4, and STXBP2 were found in 25 (14%) of the adult patients. The A91V-PRF1 genotype was found in 12 of these patients (48%). The preponderance of hypomorphic mutations in familial HLH-causing genes correlates with the later-onset clinical symptoms and the more indolent course in adult patients. We conclude that late-onset familial HLH occurs more commonly than was suspected previously.
Full Text
Duke Authors
Cited Authors
- Zhang, K; Jordan, MB; Marsh, RA; Johnson, JA; Kissell, D; Meller, J; Villanueva, J; Risma, KA; Wei, Q; Klein, PS; Filipovich, AH
Published Date
- November 2011
Published In
Volume / Issue
- 118 / 22
Start / End Page
- 5794 - 5798
PubMed ID
- 21881043
Pubmed Central ID
- 21881043
Electronic International Standard Serial Number (EISSN)
- 1528-0020
International Standard Serial Number (ISSN)
- 0006-4971
Digital Object Identifier (DOI)
- 10.1182/blood-2011-07-370148
Language
- eng