Li Xuejing, Cheng Yungai, Xu Dan, Cheng Beilei, Xu Yingchun, Chen Zhimin, Tang Lanfang, Wang Yingshuo
Department of Pulmonology, Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China.
Glob Med Genet. 2024 Nov 20;12(3):100007. doi: 10.1016/j.gmg.2024.100007. eCollection 2025 Sep.
X-linked hyper-IgM (X-HIGM), which results from mutations of the CD40 ligand gene (CD40LG) located on chromosome Xq26.3, is characterized by a defective T-B lymphocyte cross talk and class switch recombination (CSR). The present study aimed to evaluate the expression of CD40L and lymphocyte subsets using flow cytometry and to identify the novel genetic defect of responsible for X-HIGM in a Chinese family. We reported an X-HIGM case caused by a novel mutation in CD40LG. The expression of CD40L was absent on the surface of activated CD4 + T cells evaluated using flow cytometry. The total number of mature B cells in circulation was normal, but memory B cells were significantly decreased. In helper T cells, Th2 was dominant, and the numbers of Th1 and Th17 were decreased. The results of genetic analysis revealed a new causative mutation in CD40L (NM_000074;exon5;c.505_506del), which leads to a change in amino acids (p.Y169Lfs*31) appearing in the proband. The frame shift mutation led to incorrect amino acid translation and loss of β-pleated sheet and loop region, which produced a mutant dysfunctional protein. This study provides a complete picture of X-HIGM and broadens our knowledge of the pathogenicity of the CD40L variant spectrum.
X连锁高IgM综合征（X-HIGM）由位于Xq26.3染色体上的CD40配体基因（CD40LG）突变引起，其特征是T-B淋巴细胞相互作用缺陷和类别转换重组（CSR）缺陷。本研究旨在通过流式细胞术评估CD40L的表达和淋巴细胞亚群，并确定一个中国家系中导致X-HIGM的新的基因缺陷。我们报告了1例由CD40LG新突变引起的X-HIGM病例。通过流式细胞术评估发现，活化的CD4 + T细胞表面不存在CD40L表达。循环中成熟B细胞总数正常，但记忆B细胞显著减少。在辅助性T细胞中，Th2占主导，Th1和Th17细胞数量减少。基因分析结果显示，先证者中CD40L（NM_000074；外显子5；c.505_506del）出现新的致病突变，导致氨基酸改变（p.Y169Lfs*31）。移码突变导致氨基酸翻译错误，β折叠片层和环区缺失，产生功能异常的突变蛋白。本研究全面呈现了X-HIGM，并拓宽了我们对CD40L变异谱致病性的认识。
