ArticleJournal of medical genetics2006
Novel Munc13-4 mutations in children and young adult patients with haemophagocytic lymphohistiocytosis.
Article in Journal of medical genetics, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 87 citations in OpenAlex.
- Two Cases of CLIPPERS-like Syndrome Sharing a Hypomorphic UNC13D Variant.Journal of clinical immunology · 2026Article
- Case Report: Munc13-4 deficiency presenting with autoimmune neuropathy years before FLH: implications for early genetic screening and HSCT timing.Frontiers in immunology · 2026Article
- Functional role of UNC13D in immune diseases and its therapeutic applications.Frontiers in immunology · 2024Review
- Genetics of Primary Hemophagocytic Lymphohistiocytosis.Advances in experimental medicine and biology · 2024Review
- UNC13D inhibits STING signaling by attenuating its oligomerization on the endoplasmic reticulum.EMBO reports · 2022Article
- Neuroinflammation Associated With Inborn Errors of Immunity.Frontiers in immunology · 2021Review
- Frequency and spectrum of disease-causing variants in 1892 patients with suspected genetic HLH disorders.Blood advances · 2020Article
- Genotype characteristics and immunological indicator evaluation of 311 hemophagocytic lymphohistiocytosis cases in China.Orphanet journal of rare diseases · 2020Article
- Fatal unexpected death due to familial hemophagocytic lymphohistiocytosis type 3.Forensic science, medicine, and pathology · 2018Article
- Molecular Classification of Primary Immunodeficiencies of T Lymphocytes.Advances in immunology · 2018Review
- Inducible T Cell Kinase Regulates the Acquisition of Cytolytic Capacity and Degranulation in CD8Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Two Brothers with AtypicalFrontiers in immunology · 2017Article
- Altered gene expression and possible immunodeficiency in cases of sudden infant death syndrome.Pediatric research · 2016Article
- Progressive neurologic disorder: Initial manifestation of hemophagocytic lymphohistiocytosis.Neurology · 2016Article
- Genetic predisposition to hemophagocytic lymphohistiocytosis: Report on 500 patients from the Italian registry.The Journal of allergy and clinical immunology · 2016Article
- Synergistic defects of UNC13D and AP3B1 leading to adult hemophagocytic lymphohistiocytosis.International journal of hematology · 2015Article
- Human immunodeficiency syndromes affecting human natural killer cell cytolytic activity.Frontiers in immunology · 2014Review
- Familial hemophagocytic lymphohistiocytosis: when rare diseases shed light on immune system functioning.Frontiers in immunology · 2014Review
- Regulation of vesicular trafficking and leukocyte function by Rab27 GTPases and their effectors.Journal of leukocyte biology · 2013Review
- Crucial role of the hydrophobic pocket region of Munc18 protein in mast cell degranulation.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
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Authors and funding
16 authors at 6 institutions in 1 country.
Funding
Abstract
Familial haemophagocytic lymphohistiocytosis (FHL) is a genetically heterogeneous disorder characterised by constitutive defects in cellular cytotoxicity resulting in fever, hepatosplenomegaly and cytopenia, and the outcome is fatal unless treated by chemoimmunotherapy followed by haematopoietic stem-cell transplantation. Since 1999, mutations in the perforin gene giving rise to this disease have been identified; however, these account only for 40% of cases. Lack of a genetic marker hampers the diagnosis, suitability for transplantation, selection of familial donors, identification of carriers, genetic counselling and prenatal diagnosis. Mutations in the Munc13-4 gene have recently been described in patients with FHL. We sequenced the Munc13-4 gene in all patients with haemophagocytic lymphohistiocytosis not due to PRF1 mutations. In 15 of the 30 families studied, 12 novel and 4 known Munc13-4 mutations were found, spread throughout the gene. Among novel mutations, 2650C-->T introduced a stop codon; 441del A, 532del C, 3082del C and 3226ins G caused a frameshift, and seven were mis sense mutations. Median age of diagnosis was 4 months, but six patients developed the disease after 5 years of age and one as a young adult of 18 years. Involvement of central nervous system was present in 9 of 15 patients, activity of natural killer cells was markedly reduced or absent in 13 of 13 tested patients. Chemo-immunotherapy was effective in all patients. Munc13-4 mutations were found in 15 of 30 patients with FHL without PRF1 mutations. Because these patients may develop the disease during adolescence or even later, haematologists should include FHL2 and FHL3 in the differential diagnosis of young adults with fever, cytopenia, splenomegaly and hypercytokinaemia.
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