Spectrum mutations of PRF1, UNC13D, STX11, and STXBP2 genes in Vietnamese patients with hemophagocytic lymphohistiocytosis

Abstract

Introduction: The prevalence of gene mutations in hemophagocytic lymphohistiocytosis (HLH) varied between studies. Thus far, data on the genetic background of HLH in Vietnamese patients are limited.

Methods: We recruited 94 HLH patients and analyzed for the 4 genes using Sanger sequencing technology.

Results: Pathogenic variants were observed in 36 (38.29%) patients, including 27 in UNC13D, 5 in STXBP2, 3 in PRF1, and 2 in STX11 (one patient with digenic variants in both UNC13D and STX11). Monoallelic variants accounted for 77.8% of all cases with mutation. A total of 23 different types of pathogenic variants were documented in the 4 genes tested, including 15 in UNC13D, 3 in PRF1, 3 in STXBP2, and 2 in STX11. Interestingly, the novel splicing variant c.3151G>A in UNC13D was recurrently identified in 8 unrelated patients.

Conclusion: Vietnamese patients with HLH showed a distinct genetic variant spectrum, in which UNC13D is the predominant genetic lesion associated with HLH.

Keywords: PRF1; STX11; STXBP2; UNC13D; vietnamese.