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A novel 268 kb deletion combined with a splicing variant in IL7R causes of severe combined immunodeficiency in a Chinese family: a case report.

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  • Additional Information
    • Source:
      Publisher: BioMed Central Country of Publication: England NLM ID: 101319628 Publication Model: Electronic Cited Medium: Internet ISSN: 1755-8794 (Electronic) Linking ISSN: 17558794 NLM ISO Abbreviation: BMC Med Genomics Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : BioMed Central
    • Subject Terms:
      Severe Combined Immunodeficiency*/genetics ; Severe Combined Immunodeficiency*/diagnosis ; Severe Combined Immunodeficiency*/therapy ; Virus Diseases*; Infant, Newborn ; Female ; Humans ; Child ; Infant ; Retrospective Studies ; Exome ; China ; Interleukin-7 Receptor alpha Subunit/genetics
    • Abstract:
      Background: Severe combined immunodeficiency (SCID) is a group of fatal primary immunodeficiencies characterized by the severe impairment of T-cell differentiation. IL7R deficiency is a rare form of SCID that usually presents in the first months of life with severe and opportunistic infections, failure to thrive, and a high risk of mortality unless treated. Although recent improvements in early diagnosis have been achieved through newborn screening, few IL7R-related SCID patients had been reported in the Chinese population.
      Case Presentation: Here, we retrospectively analyzed a case of SCID in a 5-month-old girl with symptoms, including severe T-cell depletion, recurrent fever, oral ulcers, pneumonia, hepatosplenomegaly, bone marrow hemophagocytosis, and bacterial and viral infections. Whole-exome sequencing (WES), quantitative PCR (qPCR), and chromosome microarray analysis (CMA) were performed to identify the patient's genetic etiology. We identified a 268 kb deletion and a splicing variant, c.221 + 1G > A, in the proband. These two variants of IL7R were inherited from the father and mother.
      Conclusions: To our knowledge, this is the first report of whole IL7R gene deletion in combination with a pathogenic splicing variant in a patient with SCID. This deletion also expands the pathogenic variation spectrum of SCID caused by IL7R. The incorporation of exome-based copy number variant analysis makes WES a powerful molecular diagnostic technique for the clinical diagnosis of pediatric patients.
      (© 2023. The Author(s).)
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    • Grant Information:
      2020KY890 the Medical and Health Project of Zhejiang Province; 2023Z178 the Ningbo Key Technology Research and Development Project; 202002N3150 the Science and Technology Development Program of Ningbo; 2022020405 the Innovation Project of Distinguished Medical Team in Ningbo
    • Contributed Indexing:
      Keywords: Chromosome microarray analysis; IL7R; Severe combined immunodeficiency; Splicing variant; Whole exome sequencing
    • Accession Number:
      0 (IL7R protein, human)
      0 (Interleukin-7 Receptor alpha Subunit)
    • Publication Date:
      Date Created: 20231212 Date Completed: 20231216 Latest Revision: 20240110
    • Publication Date:
      20250114
    • Accession Number:
      PMC10712040
    • Accession Number:
      10.1186/s12920-023-01765-8
    • Accession Number:
      38082310