ArticleBlood advances2020
Frequency and spectrum of disease-causing variants in 1892 patients with suspected genetic HLH disorders.
Article in Blood advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 3 of them syntheses that pooled it.
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Who cites it
40 citing papers in PubMed, 3 syntheses or guidelines pooled it, 70 citations in OpenAlex.
- Evaluating whole genome sequencing for rare diseases in newborn screening: evidence synthesis from a series of systematic reviews.Health technology assessment (Winchester, England) · 2025Pooled it
- HLH and Recurrent EBV Lymphoma as the presenting manifestation of MAGT1 Deficiency: A Systematic Review of the Expanding Disease Spectrum.Journal of clinical immunology · 2024Pooled it
- HLH as an additional warning sign of inborn errors of immunity beyond familial-HLH in children: a systematic review.Frontiers in immunology · 2024Pooled it
- Spectrum of Primary Hemophagocytic Lymphohistiocytosis-Associated Gene Mutations in Chinese Patients.MedComm · 2026Article
- Reactive and therapy induced bone marrow changes linked to systemic infectious and non-infectious disorders including MAS/HLH report from the European association for haematopathology, Dubrovnik 2024.Virchows Archiv : an international journal of pathology · 2026Article
- Early management of hemophagocytic lymphohistiocytosis/macrophage activation syndrome: a systematic literature review.EULAR rheumatology open · 2026Review
- Two Cases of CLIPPERS-like Syndrome Sharing a Hypomorphic UNC13D Variant.Journal of clinical immunology · 2026Article
- Histiocytoses and reactive proliferations of histiocytes: current state of the art and evolving concepts-a report from the joint CSHP-EA4HP-SH workshop 2024, Hefei, China.Virchows Archiv : an international journal of pathology · 2026Review
- Genetic and molecular approaches for patients with familial hemophagocytic lymphohistiocytosis: a multi-center experience from Mexico.Frontiers in immunology · 2026Article
- Analysis of genes involved in immune response in children with HLH - case series.Pediatric rheumatology online journal · 2025Article
- Article
- Effect of genetic mutations on outcomes of stem cell transplantation in children with hemophagocytic lymphohistiocytosis.Bone marrow transplantation · 2025Article
- Clinicopathological and Immunogenetic Characterization in 8 Patients with Familial Hemophagocytic Lymphohistiocytosis Type 2: A Study from North India with Literature Review.Journal of clinical immunology · 2025Review
- Childhood Langerhans cell histiocytosis hematological involvement: severity associated with BRAFV600E loads.Blood · 2025Article
- Treating and triggering hyperinflammation: tackling hemophagocytic lymphohistiocytosis and HLH-like syndromes in the pediatric cell therapy and critical care setting.Frontiers in oncology · 2025Review
- Pancytopenia With Subsequent Diagnosis of Hemophagocytic Lymphohistiocytosis in a Middle-Aged Male.Case reports in oncological medicine · 2025Article
- The performance of sCD25 and CTLs degranulation test for screening patients with primary hemophagocytic lymphohistiocytosis: a large-scale multicenter study in China.Frontiers in immunology · 2025Article
- Hemophagocytic Lymphohistiocytosis Gene Variants in Severe Aplastic Anemia and Their Impact on Hematopoietic Cell Transplantation Outcomes.Transplantation and cellular therapy · 2024Article
- Genetic Testing in Patients with Autoimmune Lymphoproliferative Syndrome: Experience of 802 Patients at Cincinnati Children's Hospital Medical Center.Journal of clinical immunology · 2024Article
- Spectrum ofJournal of medical genetics · 2024Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
This article explores the distribution and mutation spectrum of potential disease-causing genetic variants in hemophagocytic lymphohistiocytosis (HLH)-associated genes observed in a large tertiary clinical referral laboratory. Samples from 1892 patients submitted for HLH genetic analysis were studied between September 2013 and June 2018 using a targeted next-generation sequencing panel approach. Patients ranged in age from 1 day to 78 years. Analysis included 15 genes associated with HLH. A potentially causal genetic finding was observed in 227 (12.0%) samples in this cohort. A total of 197 patients (10.4%) had a definite genetic diagnosis. Patients with pathogenic variants in familial HLH genes tended to be diagnosed significantly younger compared with other genes. Pathogenic or likely pathogenic variants in the PRF1 gene were the most frequent. However, mutations in genes associated with degranulation defects (STXBP2, UNC13D, RAB27A, LYST, and STX11) were more common than previously appreciated and collectively represented >50% of cases. X-linked conditions (XIAP, SH2D1A, and MAGT1) accounted for 17.8% of the 197 cases. Pathogenic variants in the SLC7A7 gene were the least encountered. These results describe the largest cohort of genetic variation associated with suspected HLH in North America. Merely 10.4% of patients were identified with a clearly genetic cause by this diagnostic approach; other possible etiologies of HLH should be investigated. These results suggest that careful thought should be given regarding whether patients have a clinical phenotype most consistent with HLH vs other clinical and disease phenotypes. The gene panel identified known pathogenic and novel variants in 10 HLH-associated genes.
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