STXBP2 mutations in children with familial haemophagocytic lymphohistiocytosis type 5.
Summary of "STXBP2 mutations in children with familial haemophagocytic lymphohistiocytosis type 5."
Background Familial haemophagocytic lymphohistiocytosis (FHL) is a rare immune deficiency with uncontrolled inflammation; the clinical course usually starts within the first years of life, and is usually fatal unless promptly treated and then cured with haematopoietic stem cell transplant. FHL is caused by genetic mutations resulting in defective cell cytotoxicity; three disease related genes have been identified to date: perforin, Munc13-4 and syntaxin-11. A fourth gene, STXBP2, has been identified very recently as responsible for a defect in Munc18-2 in FHL-5. Aims To describe the result of the screening of families with HLH and previously unassigned genetic defects. Methods Patients with HLH diagnosed according to current diagnostic criteria, and who lacked mutations in the PRF1, Munc13-4, and STX11 genes were sequenced for mutations in STXBP2. Functional study was performed when material was available. Results Among the 28 families investigated, 4 (14%) with biallelic STXBP2 mutations were identified. They originated from Italy, England, Kuwait and Pakistan. The p.Pro477Leu resulting from c.1430C>T, and p.Arg405Gln resulting from the single c.1214G>A nucleotide change are known, while we contribute two novel mutations: p.Glu132Ala resulting from c.395A>C, and p.Gly541Ser, resulting from c.1621G>A. The detrimental effect of the p.Gly541Ser mutation was documented biochemically and functionally in NK and CD8 cells. Additional polymorphisms are also described. Conclusion These data expand current knowledge on the genetic heterogeneity of FHL and suggest that patients with FHL5 may have different results in degranulation assays under different conditions.
24 50139 Firenze, Italy; firstname.lastname@example.org.
This article was published in the following journal.
Name: Journal of medical genetics
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20798128
- DOI: http://dx.doi.org/10.1136/jmg.2009.075341
The mutations in UNC13D are responsible for familial hemophagocytic lymphohistiocytosis (FHL) type 3. A 253-kb inversion and two deep intronic mutations, c.118-308C > T and c.118-307G > A, in...
Mutations of PRF1 gene have been identified in familial hemophagocytic lymphohistiocytosis type-2 (FHL-2) patients, and it has been reported as the commonest gene defect causing FHL. Patients with sev...
Haemophagocytic lymphohistiocytosis (HLH) is a potentially fatal, hyper inflammatory condition which is caused by a highly stimulated but ineffective immune response. We are presenting here, a case of...
Hemophagocytic lymphohistiocytosis (HLH) occurs in the primary form (genetic or familial) or secondary form (acquired). The familial form of HLH (FHL) is a potentially fatal autosomal recessive disord...
Neurologic symptoms can be the initial manifestation of haemophagocytic lymphohistiocytosis (HLH). In this case study, we present a 3-year old boy with a clinical picture of encephalitis, a cerebrospi...
Hemophagocytic lymphohisticytosis (HLH) is a rare and severe disease of genetic origin in children (familial-HLH, F-HLH) or affecting adults secondary to infections, hematologic malignanci...
The aim of the present study is to explore functional consequences of migraine gene mutations on their responses to Calcitonin Gene Related Peptide (CGRP)infusion.
Without therapy HLH is often fatal, and often rapidly fatal. The treatment protocol HLH-94 has improved survival markedly as compared to the survival earlier. We now aim to improve surviva...
Mutations of the ATP binding cassette subfamily B member 4 (ABCB4) gene, a gene involved in a subtype of progressive familial intrahepatic cholestasis, have been reported in women sufferin...
Despite good progress during the last decade, hemophagocytic ymphohistiocytosis (HLH) remains difficult to treat. Two different treatment regimens have been used successfully. The first o...
Medical and Biotech [MESH] Definitions
A group of related disorders characterized by LYMPHOCYTOSIS; HISTIOCYTOSIS; and hemophagocytosis. The two major forms are familial and reactive.
Familial pseudoaldosteronism characterized by autosomal dominant inheritance of hypertension with HYPOKALEMIA; ALKALOSIS; RENIN and ALDOSTERONE level decreases. It is caused by mutations in EPITHELIAL SODIUM CHANNEL beta and gamma subunits. Different mutations in the same EPITHELIAL SODIUM CHANNEL subunits can cause PSEUDOHYPOALDOSTERONISM, TYPE I, AUTOSOMAL DOMINANT.
A severe type of hyperlipidemia, sometimes familial, that it is characterized by the elevation of both plasma CHYLOMICRONS and TRIGLYCERIDES contained in VERY-LOW-DENSITY LIPOPROTEINS. Type V hyperlipoproteinemia is often associated with DIABETES MELLITUS and is not caused by reduced LIPOPROTEIN LIPASE activity as in HYPERLIPOPROTEINEMIA TYPE I .
A type of familial lipid metabolism disorder characterized by a variable pattern of elevated plasma CHOLESTEROL and/or TRIGLYCERIDES. Multiple genes on different chromosomes may be involved, such as the major late transcription factor (UPSTREAM STIMULATORY FACTORS) on CHROMOSOME 1.
A multisystem disorder that is characterized by aplasia of intrahepatic bile ducts (BILE DUCTS, INTRAHEPATIC), and malformations in the cardiovascular system, the eyes, the vertebral column, and the facies. Major clinical features include JAUNDICE, and congenital heart disease with peripheral PULMONARY STENOSIS. Alagille syndrome may result from heterogeneous gene mutations, including mutations in JAG1 on CHROMOSOME 20 (Type 1) and NOTCH2 on CHROMOSOME 1 (Type 2).