Spectrum, and clinical and functional implications of UNC13D mutations in familial haemophagocytic lymphohistiocytosis

@article{Rudd2007SpectrumAC,
  title={Spectrum, and clinical and functional implications of UNC13D mutations in familial haemophagocytic lymphohistiocytosis},
  author={Eva Rudd and Yenan T. Bryceson and C Zheng and Josefine Edner and Stephanie M. Wood and Kim G{\"o}ransdotter Ramme and Sofie Gavhed and Aytemiz G{\"u}rgey and Marit Hellebostad and Anne Grete Bechensteen and H G Ljunggren and Bengt Fadeel and Magnus Nordenskj{\"o}ld and Jan-Inge Henter},
  journal={Journal of Medical Genetics},
  year={2007},
  volume={45},
  pages={134 - 141}
}
Objective: Familial haemophagocytic lymphohistiocytosis (FHL) is a fatal disorder of immune dysregulation with defective cytotoxic lymphocyte function. Disease-causing mutations have been identified in the genes encoding perforin (PRF1), syntaxin-11 (STX11), and Munc13-4 (UNC13D). We screened for UNC13D mutations and studied clinical and functional implications of such mutations in a well defined patient cohort. Methods: Sequencing of UNC13D was performed in 38 FHL patients from 34 FHL families… 
UNC13D is the predominant causative gene with recurrent splicing mutations in Korean patients with familial hemophagocytic lymphohistiocytosis
TLDR
The identification of mutations missed by conventional sequencing would better delineate the mutation spectrum and help to establish the optimal molecular diagnostic strategy for familial hemophagocytic lymphohistiocytosis in Korea, which might need an RNA-based screening strategy.
Multiple inherited sequence variations in two disease‐causing genes in familial haemophagocytic lymphohistiocytosis
TLDR
Two cases of FHL with central nervous system (CNS) involvement and concurrent inheritance of homozygous mutations in two different disease-causing genes (UNC13D and STX11) are reported.
Familial hemophagocytic lymphohistiocytosis type 3 (FHL3) caused by deep intronic mutation and inversion in UNC13D.
TLDR
Findings implicate an intronic sequence in cell-type specific expression of Munc13-4 and signify variations outside exons and splice sites as a common cause of FHL3, which is an autosomal recessive, often-fatal hyperinflammatory disorder.
Clinical and genetic characteristics in a series of haemophagocytic lymphohistiocytosis patients without perforin defects
TLDR
UNC13D mutations were found in 50% of the HLH families without perforin defects and STX11 defects were not detected, supporting a heterogeneous genetic background for this disease.
Variations of the UNC13D Gene in Patients with Autoimmune Lymphoproliferative Syndrome
TLDR
This work sequenced UNC13D in 21 ALPS and 20 DALD patients and compared these results with sequences obtained from 61 healthy subjects and 38 multiple sclerosis patients to suggest that rare loss-of-function variations of UND13D are risk factors for ALPS development.
Spectrum of clinical presentations in familial hemophagocytic lymphohistiocytosis type 5 patients with mutations in STXBP2.
TLDR
Familial HLH type 5 is associated with a spectrum of clinical symptoms, which may be a reflection of impaired expression and function of Munc18-2 also in cells other than cytotoxic lymphocytes, and mutations in STXBP2 should thus also be considered in patients with clinical manifestations other than those typically associated with HLH.
Familial hemophagocytic lymphohistiocytosis type 5 (FHL-5) is caused by mutations in Munc18-2 and impaired binding to syntaxin 11.
TLDR
A key role is identified for STXBP2 in lytic granule exocytosis in FHL-5 patients, where activity of natural killer and cytotoxic T cells was markedly reduced or absent, as determined by CD107 degranulation.
Exome sequencing for simultaneous mutation screening in children with hemophagocytic lymphohistiocytosis
TLDR
Exome sequencing demonstrated the ability to identify rare genetic variants in HLH patients and is useful in the detection of mutations in multi-gene associated diseases.
Unusual functional manifestations of a novel STX11 frameshift mutation in two infants with familial hemophagocytic lymphohistiocytosis type 4 (FHL4)
TLDR
Unexpectedly, degranulation by NK cells from one of the patients was not impaired, although patient NK cells showed mildly and significantly decreased cytotoxicity, respectively, implying that STX11 should be sequenced in HLH patients even when impaired NK cell de granulation is not found.
Clinical, immunological and genetic findings in patients with UNC13D deficiency (FHL3): A systematic review
  • P. Amirifar, M. Ranjouri, +6 authors R. Yazdani
  • Medicine
    Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology
  • 2020
Familial hemophagocytic lymphohistiocytosis (FHL) is a rare autosomal recessive immune disorder that is caused by mutations in 6 different genes related to the formation and function of secretory
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TLDR
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TLDR
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TLDR
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