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

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.We recruited 94 HLH patients and analyzed for the 4 genes using Sanger sequencing technology.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.Vietnamese patients with HLH showed a distinct genetic variant spectrum, in which UNC13D is the predominant genetic lesion associated with HLH.