Track topics on Twitter Track topics that are important to you
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
We retrospectively analysed charts of patients with blood ferritin level >5000 µg/l. The aim of the study was to look for the likelihood of haemophagocytic lymphohistiocytosis (HLH) in these patients...
Patients with inflammatory bowel disease (IBD) are at risk of developing haemophagocytic lymphohistiocytosis (HLH) because of chronic systemic inflammation as well as exposure to immunosuppressive med...
Cerebellar swelling with obstructive hydrocephalus is a rare but life threatening condition, associated with different etiologies, familial hemophagocytic lymphohistiocytosis (HLH) being rarely one of...
To investigate the association between rs1799864 single nucleotide polymorphism (SNP) of the C-C chemokine receptor 2 (CCR2) gene and susceptibility of hemophagocytic lymphohistiocytosis (HLH) in chil...
The purpose of this project is to study the number of surviving patients until hematopoietic stem cell transplantation (HSCT) after first line treatment of hemophagocytic lymphohistiocytos...
This study seeks to determine the efficacy of tocilizumab (TCZ) in patients with hemophagocytic lymphohistiocytosis (HLH) and high cytokine levels (proteins involved in inflammation) in an...
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...
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).
Pediatrics is the general medicine of childhood. Because of the developmental processes (psychological and physical) of childhood, the involvement of parents, and the social management of conditions at home and at school, pediatrics is a specialty. With ...
Organ transplantation is the moving of an organ from one body to another or from a donor site to another location on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative ...