OBJECTIVETo introduce the clinical manifestations and laboratory tests of adult onset of primary hemophagocytic syndrome (HPS), and to investigate the essentials of diagnosis and the genotype characteristics in adult onset patient.

METHODSThe definite diagnosis of HPS was made according to HLH-2004. Exons of PRF1, STX11, UNC13D, SH2D1A and RAB27A genes coding region were amplified using polymerase chain reaction.

RESULTSA 48-year-old man was admitted to our hospital because of recurrent fever, pancytopenia and lymph node enlargement. His laboratory test revealed bone marrow hemophagocytosis, elevated ferritin level (2000 µg/L), reduced level of NK cell activity (20.13%) and elevated soluble CD25 level (12277 U/ml). Based on the HLH-2004 diagnostic criteria, the patient was diagnosed as HPS. The patient had viral infection, and no other primary disease was identified that would cause HPS. The patient responded poorly to anti-viral therapy. DNA sequencing was used to confirm that perforin gene mutations might be one of the causes of the patient suffered from primary HPS.

CONCLUSIONSAlthough primary HPS usually affects infants and young children, it also occurred in teens and adults. It is essential to perform genetic screenings to patient whose illnesses recur with unknown causes. In addition, detection of molecular genetic alterations can be used to distinguish primary HPS from acquired HPS.

Humans ; Lymphohistiocytosis, Hemophagocytic ; diagnosis ; genetics ; Male ; Middle Aged ; Perforin ; genetics

Child, Preschool ; Humans ; Lymphohistiocytosis, Hemophagocytic ; diagnosis ; genetics ; therapy ; Male

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome characterized by pancytopenia and multiple organ infiltrations of lymphocytes and histiocytes with proliferation and hemohpagocytic activity. HLH is classified as primary (or familial) and secondary. Familial HLH is common in infants and young children, and is related to genetic defects. This article aims to review research advances on PRF1, UNC13D, STX11 and STXBP2, as well as the other 5 genes associated with familial HLH based on molecular genetics, and to summarize diagnosis and treatment methods for this disease.
Humans ; Lymphohistiocytosis, Hemophagocytic ; diagnosis ; etiology ; genetics ; therapy ; Molecular Biology

OBJECTIVE: To explore the genetic basis for a patient with Familial hemophagocytic lymphohistiocytosis (FHL). METHODS: A 35-day-old male infant who was admitted to the Oriental Hospital Affiliated to Xiamen University on August 3, 2021 due to fever for over 7 hours was selected as the study subject. Whole exome sequencing (WES) was carried out for the proband and his parents, and candidate variants were selected based on the clinical phenotypes of the proband and confirmed by Sanger sequencing. RESULTS: WES and Sanger sequencing results revealed that the proband had harbored compound heterozygous c.67_71delinsGCCC and c.65delC variants of the PRF1 gene, which were respectively inherited from his mother and father. The c.67_71delinsGCCC variant was unreported previously. Based on the guidelines of American College of Medical Genetics and Genomics and clinical manifestations, it was classified as pathogenic (PVS1+PM2_Supporting+PM3+PP4). c.65delC was a known pathogenic variant (PVS1+PM2_Supporting+PM3_Strong+PP4). CONCLUSION The compound heterozygous variants of c.67_71delinsGCCC and c.65delC of the PRF1 gene probably underlay the disease in the proband. The identification of the novel variant has expanded the mutational spectrum of the PRF1 gene.
Male ; Female ; Humans ; Lymphohistiocytosis, Hemophagocytic/genetics* ; Genomics ; Mothers ; Mutation ; Phenotype

OBJECTIVE: To analyze the gene polymorphisms of patients with lymphoma-associated hemophagocytic syndrome in Longyan area, Fujian province. METHODS: A total of 125 patients with lymphoma-associated hemophagocytic syndrome in Longyan, Fujian province, admitted to Longyan First Hospital from May 2017 to November 2020 were selected. Peripheral venous blood was collected from all the patients, and the genotypes of perforin 1 (PRF1) and interleukin-10 (IL-10) gene loci were detected by PCR-fluorescence probe method, and the correlation between PRF1 and IL-10 gene polymorphisms and lymphoma-associated hemophagocytic syndrome was analyzed. RESULTS: The mutation frequencies of PRF1 gene loci rs885821 (C>T), rs885822 (C>T), rs1889490 (G>A) in patients with lymphoma-associated hemophagocytic syndrome were 10.40%, 78.8% and 64.4%, respectively. The mutation frequencies of rs1800872 (A>C), rs1800871 (C>T) and rs1800896 (G>A) of IL-10 loci were 56.0%, 45.2% and 77.6%, respectively. CONCLUSION PRF1 and IL-10 gene loci were polymorphic in patients with lymphoma-associated hemophagocytic syndrome in Longyan area, Fujian province. Alleles C and G of PRF1 and IL-10 were risk factors, and alleles T and A were protective factors.
Humans ; Genotype ; Interleukin-10/genetics* ; Lymphohistiocytosis, Hemophagocytic/genetics* ; Lymphoma/genetics* ; Perforin/genetics* ; Polymorphism, Genetic

OBJECTIVETo 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 children.

METHODSThe clinical and laboratory data of 86 children diagnosed with HLH between January 2007 and December 2013 were retrospectively reviewed. The CCR2 gene rs1799864 was genotyped by SNaPshot technique in 86 HLH children and 128 healthy controls. The genotypic and allelic frequencies in the two groups were comparatively analyzed.

RESULTSNo significant difference either in genotypic or allelic frequencies of rs1799864 polymorphism of the CCR2 gene was observed between HLH patients and controls (P>0.05), but there were significant differences in the age of onset and the periods of temperature and platelet returning to normal after treatment (P<0.05).

CONCLUSIONSThere is no association between CCR2 gene rs1799864 polymorphism and the risk for HLH in children. However, the genotypic differences of this polymorphism might be associated with clinical characteristics and prognosis of HLH.

Child ; Child, Preschool ; Female ; Genotype ; Humans ; Lymphohistiocytosis, Hemophagocytic ; genetics ; Male ; Polymorphism, Single Nucleotide ; Receptors, CCR2 ; genetics

OBJECTIVETo research the relationship between human herpesvirus 7 (HHV-7) viral Load and the etiopathogenisis of hemophagocytic syndrome, in order to provide evidence for the clinical diagnosis of hemophagocytic syndrome and anti-virus therapy.

METHODSPeripheral blood of patient with hemophagocytic syndrome during different treatment periods, extracted DNA, Syntheticed the primers of HHV-7, gene sequence of PCR amplified fragments detected, determined HHV-7 viral Load by Real-time fluorescent quantitative PCR and the ferritin concentration in peripheral blood detected by chemiluminescence.

RESULTThe sequence result indicated that PCR amplified fragment was a part of HHV-7 gene, the ferritin concentration viried with the load of HHV-7.

CONCLUSIONThe occurrence of hemophagocytic syndrome is connetted with the load of HHV-7.

Ferritins ; metabolism ; Herpesvirus 7, Human ; genetics ; isolation & purification ; physiology ; Humans ; Lymphohistiocytosis, Hemophagocytic ; metabolism ; virology ; Viral Load

Humans ; Infant ; Lymphohistiocytosis, Hemophagocytic ; complications ; genetics ; pathology ; Male ; Thymus Gland ; abnormalities

Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal disease caused by dysregulated immune responses and overwhelming inflammation to infectious or other triggers of the immune system. HLH may be inherited (primary) or may be secondary to any severe infection, malignancy or rheumatologic disease. Clinical progress of HLH is usually rapid and fatal. Early recognition and assessment of potential causes of HLH is critical to improve survival. Urgent treatment is needed for immunosuppression and degradation of the activated antigen. Over the last two decades, research on genetics and pathophysiology of HLH has much improved treatment outcome of the patient. Here, we review recent advances in our understanding of etiology, pathophysiology, diagnosis and treatment of HLH.
Diagnosis ; Genetics ; Humans ; Immune System ; Immunosuppression ; Inflammation ; Lymphohistiocytosis, Hemophagocytic ; Treatment Outcome

This study was aimed to explore the pathogenesis of type III familial hemophagocytic lymphohistiocytosis (FHL3) via susceptibility gene UNC13D involving in homologous recombination repair (HRR) of DNA double-strand break (DSB). By means of DNA homologous recombination repair, the change of homologous recombination repair rate of normal control cells and DR-U2OS cells after down-regulation of UNC13D was detected; the UNC13D gene related function was explored. The results showed that DR-U2OS cells displayed a significant reduction in homologous recombination repair of DNA DSB after siRNA knockdown of UNC13D, compared to its normal control cell counterparts (P < 0.05), suggesting that UNC13D was involved in DNA double-stranded breakage repair. It is concluded that UNC13D gene mutation may be involved in the pathogenesis of FHL3 via its dual effects of both the cytotoxic granule exocytosis and decrease of homologous recombination repair rate after the DNA double-strand break, therefore, providing a new theoretical basis to reveal the pathogenesis of FHL3.
DNA Breaks, Double-Stranded ; DNA-Binding Proteins ; genetics ; Humans ; Lymphohistiocytosis, Hemophagocytic ; classification ; genetics ; Membrane Proteins ; genetics ; Recombinational DNA Repair