Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Mar 10;4(5):925-929.
doi: 10.1182/bloodadvances.2019001272.

Identification of germline variants in adults with hemophagocytic lymphohistiocytosis

Peter G Miller  1   2   3 , Abhishek Niroula  1   3 , John J Ceremsak  4 , Christopher J Gibson  1 , Martin S Taylor  5 , Sebastian Birndt  6 , Florian Perner  1 , Jon Arnason  7 , Adam S Sperling  1   3 , Mridul Agrawal  1   2 , Alison M Schram  8 , Sarah Nikiforow  1 , German Pihan  7 , Robert P Hasserjian  5 , Jon C Aster  9 , Paul La Rosée  10 , Elizabeth A Morgan  9 , Nancy Berliner  2 , Benjamin L Ebert  1   3   11
Affiliations

Identification of germline variants in adults with hemophagocytic lymphohistiocytosis

Peter G Miller et al. Blood Adv. .

Abstract

  1. Some germline variants are predicted to disrupt protein function in HLH-associated genes.

  2. Such variants are neither enriched in adult-onset HLH nor associated with specific clinical or laboratory features of HLH.

PubMed Disclaimer

Conflict of interest statement

Conflict-of-interest disclosure: B.L.E. has received research funding from Celgene and Deerfield, consulting fees from GRAIL, and is on the scientific advisory boards for Exo Therapeutics and Skyhawk Therapeutics. P.G.M. has received consulting fees from Foundation Medicine, Inc. The remaining authors declare no competing financial interests.

Figures

Figure 1.
Figure 1.
Frequency and distribution of predicted disruptive variants in the HLH cohort. (A) Schematic of germline variant frequency within cohort among 17 HLH-associated genes sequenced. (B) Frequency of total and predicted disruptive germline variants observed in FHL genes in cohort. (C) Percentage of individuals in HLH and the 1000 Genomes Project (TGP) cohort carrying variants in HLH-associated genes. TGP var indicates the percentage of individuals in the TGP cohort carrying variants identified in the HLH cohort; TGP rule indicates the percentage of individuals in the TGP cohort carrying any variants identified by the same rules as for the HLH cohort. Percentages compared whole data (HLH [n = 88] and TGP [n = 2503]) and white or Caucasian individuals (HLH [n = 68] and TGP [n = 503]). Among white or Caucasian individuals, similar analysis was performed by excluding the PRF1 A91V variant. The percentage of individuals carrying predicted disruptive variants is shown in red. *P < .05; •P ≥ .05. The significance test result for carriers of all variants is indicated in black; the same for carriers of predicted disruptive variants is shown in red. + indicates the SH2D1A R55Q mutation, which is encoded on the X chromosome, was present in a male patient.
See this image and copyright information in PMC

References

    1. Schram AM, Berliner N. How I treat hemophagocytic lymphohistiocytosis in the adult patient. Blood. 2015;125(19):2908-2914. - PubMed
    1. Brisse E, Wouters CH, Matthys P. Advances in the pathogenesis of primary and secondary haemophagocytic lymphohistiocytosis: differences and similarities. Br J Haematol. 2016;174(2):203-217. - PubMed
    1. Cetica V, Sieni E, Pende D, et al. Genetic predisposition to hemophagocytic lymphohistiocytosis: report on 500 patients from the Italian registry. J Allergy Clin Immunol. 2016;137(1):188-196.e4. - PMC - PubMed
    1. Zhang K, Jordan MB, Marsh RA, et al. Hypomorphic mutations in PRF1, MUNC13-4, and STXBP2 are associated with adult-onset familial HLH. Blood. 2011;118(22):5794-5798. - PMC - PubMed
    1. Tesi B, Lagerstedt-Robinson K, Chiang SC, et al. Targeted high-throughput sequencing for genetic diagnostics of hemophagocytic lymphohistiocytosis. Genome Med. 2015;7:130. - PMC - PubMed

Publication types