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    Home > Active Ingredient News > Blood System > Researchers have discovered a rare inherited blood disease HLH new pathogenic gene

    Researchers have discovered a rare inherited blood disease HLH new pathogenic gene

    • Last Update: 2022-09-22
    • Source: Internet
    • Author: User
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    Hemophagocytic syndrome (HLH) is a severely life-threatening rare blood disease with an incidence of only one in a million, named after
    the phenomenon of phagocytes commonly found in the bone marrow of patients.

    HLH is essentially caused by the overactivation of the immune system caused by innate or acquired factors, the secretion of excessive cytokines to form a cytokine storm, and the short period of time leading to multi-organ failure, which is life-threatening

    The etiology and pathogenesis of HLH are complex, and genetic factors are considered to be one
    of the main causes of its pathogenesis.

    According to the HLH International Diagnosis and Treatment Guidelines, patients with HLH susceptible gene mutations confirmed by genetic testing can be diagnosed with primary HLH, and hematopoietic stem cell transplantation is the only cure

    There are currently 12 HLH susceptibility genes used for clinical screening (PRF1 et al

    However, about 80% of patients do not detect these HLH gene mutations, but a considerable number of them show typical characteristics
    of primary HLH, such as familial clustering and recurrent disease.

    These patients are likely to have an undiscovered genetic abnormality that delays treatment lead to a poor prognosis

    So, in addition to the 12 HLH genes that have been discovered, are there unknown pathogenic genetic mutations? What is the molecular pathogenesis of these mutations that cause HLH?


    The team of Wang Qianfei and Liu Xin of the Beijing Institute of Genomics of the Chinese Academy of Sciences (National Bioinformatics Center) and the team of Zhang Rui of Beijing Children's Hospital affiliated to Capital Medical University focused on the above clinical problems, carried out research on the genetic variation of HLH neo-pathogens, combined with family models, genomic mutations, clinical characterization of patients and molecular biology function verification, and made a breakthrough discovery of HLH new pathogenic genes
    that are conducive to clinical practical application.

    The research results were recently published in the Journal of Hematology & Oncology under the title NBAS, a gene involved in cytotoxic degranulation, is recurrently mutated in pediatric hemophagocytic lymphohistiocytosis



    The research team conducted genome-wide or exome-wide sequencing of 13 children and their parents in highly suspected primary HLH patients who did not carry known disease-causing mutations, and locked potential causative factors to the NBAS gene
    with repeated mutations in patients through bioinformatics analysis.

    The researchers further validated the reproducibility of NBAS gene mutations in the Chinese HLH cohort (224 children with sporadic HLH) and found that the mutation incidence rate (2.
    11%) was only lower than that of the most common HLH mutation gene PRF1 (3.

    Through the patient's primary cell phenotype and in vitro cell line function experiments, it was confirmed that NBAS gene defects may produce HLH by causing cytotoxic dysfunction of immune cells such as NK



    Based on a large sample of HLH-affected people in China, combined with a family model to conduct in-depth research on children with HLH with obvious genetic defects, the new pathogenic gene NBAS of HLH was discovered for the first time in the world, and combined with functional experiments to reveal the intrinsic molecular mechanism
    of the gene in HLH.

    The research results expand people's understanding of the pathogenesis of HLH, and NBAS is expected to become the 13th HLH clinical diagnosis gene, which will eventually help clinically screen high-risk groups of HLH and help improve the rate
    of early diagnosis and treatment of patients.



    The research has been funded
    by the National Key Research and Development Program, the National Natural Science Foundation of China, and the Beijing Municipal Natural Science Foundation.

    A hypothetical model of NBAS gene defects causing HLH to occur

    Source: Beijing Institute of Genomics, Chinese Academy of Sciences

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