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国内首例FOXN1单倍体不足报告并文献复习

李文道,  谷昊,  王薇,  吴润晖,  宋红梅

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文章导航 > 协和医学杂志  > 2022 > 优先出版
李文道, 谷昊, 王薇, 吴润晖, 宋红梅. 国内首例FOXN1单倍体不足报告并文献复习[J]. 协和医学杂志. doi: 10.12290/xhyxzz.2022-0040
引用本文: 李文道, 谷昊, 王薇, 吴润晖, 宋红梅. 国内首例FOXN1单倍体不足报告并文献复习[J]. 协和医学杂志. doi: 10.12290/xhyxzz.2022-0040
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LI Wendao, GU Hao, WANG Wei, WU Runhui, SONG Hongmei. First Case Report of FOXN1 Haploinsufficiency in China and Literature Review[J]. Medical Journal of Peking Union Medical College Hospital. doi: 10.12290/xhyxzz.2022-0040
Citation: LI Wendao, GU Hao, WANG Wei, WU Runhui, SONG Hongmei. First Case Report of FOXN1 Haploinsufficiency in China and Literature Review[J]. Medical Journal of Peking Union Medical College Hospital. doi: 10.12290/xhyxzz.2022-0040
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国内首例FOXN1单倍体不足报告并文献复习

doi: 10.12290/xhyxzz.2022-0040

  • 1 中国医学科学院北京协和医院儿科, 北京 100730;

  • 2 国家儿童医学中心, 首都医科大学附属北京儿童医院血液病中心, 儿童血液病与肿瘤分子分型北京市重点实验室, 儿科学国家重点学科儿科重大疾病研究教育部重点实验室, 北京 100045

基金项目: 

国家重点研发计划(2021YFC2702000)；国家科技资源共享服务平台计划(YCZYPT[2020]01)

详细信息
    通讯作者:

    吴润晖，E-mail：runhuiwu@hotmail.com

    宋红梅，E-mail：songhm1021@126.com

  • 中图分类号: R593.3;R725.9

First Case Report of FOXN1 Haploinsufficiency in China and Literature Review

  • 1 Department of Pediatrics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China;

  • 2 Hematology Oncology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China

Funds: 

National Key R&D Program of China(2021YFC2702000)

    摘要
  • 摘要: 目的 报道国内首例FOXN1单倍体不足患儿的临床及免疫学特点，并总结国外既往报道病例特征。 方法 回顾性分析1例FOXN1单倍体不足患儿的临床表现、全外显子组测序结果，并对T细胞抗原受体剪切环（T cell receptor rearrangement excisioncircles，TRECs）和κ-删除重组切除环（κ-deleting recombination excision circles，κ RECs）水平、TB细胞亚群及T细胞受体（T cell receptor，TCR） Vβ多样性进行检测。以“ FOXN1 deficiency”“ FOXN1 haploinsufficiency”“ FOXN1缺陷”“ FOXN1单倍体不足”为检索词，检索PubMed、万方数据知识服务平台和中国知网，并进行文献复习。 结果 患儿，女婴，1岁5个月，以反复自身免疫性溶血性贫血为主要表现，伴毛发稀疏、甲营养不良。基因检测提示FOXN1基因c.1392_1401delTCCTGGACCC（p.P465Rfs*82）新生杂合突变，诊断为FOXN1单倍体不足。TRECs检测提示T细胞生成缺陷，KRECs正常，TCR Vβ显示TCR多样性受限。TB细胞分群提示CD4+ T细胞减少，初试CD4+ T减少，以记忆型CD4+ T细胞为主。共检索到5篇相关文献，均为英文文献。目前，全球共报道41例FOXN1单倍体不足患儿，突变类型以移码突变为主。 结论 FOXN1单倍体不足是联合免疫缺陷病的一种，以婴幼儿期T细胞减少、反复感染为主要表现，可伴毛发发育异常、甲营养不良及自身免疫现象，骨髓移植不能治愈该疾病。
    Abstract: Objective To analyze the clinical and immunological characteristics of first case of FOXN1 haploinsufficiency in China and summarize the clinical characteristics of previous reported cases in other countries. Methods The whole-exome sequencing(WES) and Sanger sequencing were conducted to verify the mutation of FOXN1.The T cell receptor rearrangement excision circles(TRECs) and κ -deleting recombination excision circles(κ RECs) copies, peripheral blood lymphocyte subsets and T cell receptor (TCR) Vβ repertoire were further detected。A literature search was conducted using PubMed, Wangfang Med Online and CNKI with search terms "FOXN1 deficiency", "FOXN1 haploinsufficiency". Results A 1-year-old girl manifested with recurrent autoimmune hemolytic anemia, hair loss and nail dystrophy. Genetic mutation of FOXN1 (c.1392_1401delTCCTGGACCC, p.P465Rfs*82) was confirmed by WES and Sanger sequencing. The TRECs were 0.35copies/μ L, κ RECs were normal. The TCR Vβ repertoire in this patient was markedly oligoclonal. Lymphocytes subsets revealed a predominate decrease of CD4+ T cell and NaïveCD4+ T, an increase of effector memory helper T cells. A total of 5 publications were included (5 English and 0 Chinese). Thus far, 41 cases have been reported in the worldwide who mostly manifested with the decrease of T cells in early child. Conclusion FOXN1 haploinsufficiency deficiency is a kind of combined immunodeficiency disease, which is mainly manifested by the decrease of T cells and repeated infection in infants and young children, and may also accompanied by hair loss, nail dystrophy and autoimmune disease, which cannot be cured by hematopoietic stem cell transplantation.
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    • 参考文献(27)
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出版历程
  • 收稿日期:  2022-01-27
  • 录用日期:  2022-02-22
  • 网络出版日期:  2022-08-22

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