Mutation spectrum in children with primary hemophagocytic lymphohistiocytosis: molecular and functional analyses of PRF1, UNC13D, STX11, and RAB27A

@article{Stadt2006MutationSI,
  title={Mutation spectrum in children with primary hemophagocytic lymphohistiocytosis: molecular and functional analyses of PRF1, UNC13D, STX11, and RAB27A},
  author={Udo zur Stadt and Karin Beutel and Susanne Kolberg and Reinhard Schneppenheim and Hartmut Kabisch and Gritta E Janka and Hans Christian Hennies},
  journal={Human Mutation},
  year={2006},
  volume={27}
}
Familial hemophagocytic lymphohistiocytosis (FHL) is an autosomal‐recessive disease that affects young children. It presents as a severe hyperinflammatory syndrome with activated macrophages and T lymphocytes. Mutations in the perforin 1 gene (PRF1) were found in FHL‐2 in 15–50% of all cases. Defective granule exocytosis caused by mutations in the hMunc13‐4 gene (UNC13D) has been described in FHL‐3. FHL‐4 patients have mutations in STX11, a t‐SNARE involved in intracellular trafficking. We… 
Spectrum, and clinical and functional implications of UNC13D mutations in familial haemophagocytic lymphohistiocytosis
TLDR
Familial haemophagocytic lymphohistiocytosis should be considered not only in infants but also in adolescents, and possibly young adults, presenting with fever, splenomegaly, cytopenia, hyperferritinaemia, and/or CNS symptoms.
Genotype–phenotype study of familial haemophagocytic lymphohistiocytosis due to perforin mutations
TLDR
Genotype–phenotype analysis, previously hampered by limited numbers of patients, was for the first time performed by data pooling from five large centres worldwide, finding specific mutations are strongly associated with Turkish, African American and Japanese ethnic groups.
The Spectrum of Clinical, Immunological, and Molecular Findings in Familial Hemophagocytic Lymphohistiocytosis: Experience From India
TLDR
A retrospective analysis of 101 molecularly characterized FHL patients over the last 10 years from 20 different referral centers in India reveals a wide genetic heterogeneity of FHL in the Indian population and confirms the poor prognosis of F HL.
Characterization of PRF1, STX11 and UNC13D genotype‐phenotype correlations in familial hemophagocytic lymphohistiocytosis
TLDR
It is indicated that the disease‐causing mutations in FHL have different phenotypes with regard to ethnic origin, age at onset, and pathological CSF at diagnosis.
RF1 Gene Mutation in Familial Hemophagocytic Lymphohistiocytosis 2: A Family Report and Literature Review
Objective Gene mutation analysis was performed on a family with familial hemophagocytic lymphohistiocytosis (FHL) so as to provide an accurate etiological diagnosis, leading to genetic counseling for
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.
A Novel Compound Heterozygous Stxbp2 Mutation in a Case with Familial Hemophagocytic Lymphohistiocytosis
TLDR
The STXBP-2 (FHLH 5) mutation is a poor prognosis HLH type frequently seen in infants after gastroenteritis and is detected in a six-month-old infant presenting with acute hepatitis and meeting the HLH diagnostic criteria.
Novel Munc13–4 mutations in children and young adult patients with haemophagocytic lymphohistiocytosis
TLDR
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.
Spectrum of perforin gene mutations in familial hemophagocytic lymphohistiocytosis (FHL) patients in India.
TLDR
A wide heterogeneity was observed in the nature of mutations in Indian FHL2 patients and molecular characterization of PRF1 gene was not only used in the confirmation of diagnosis but also in genetic counseling and pre-natal diagnosis in affected families.
STXBP2 mutations in children with familial haemophagocytic lymphohistiocytosis type 5
TLDR
Current knowledge on the genetic heterogeneity of FHL is expanded and it is suggested that patients with FHL5 may have different results in degranulation assays under different conditions.
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TLDR
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TLDR
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TLDR
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TLDR
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