邮件订阅 RSS

留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

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

downloadPDF
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
shu
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
shu

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.
    • HTML全文
    • 参考文献(27)
  • [1] Bosticardo M, Yamazaki Y, Cowan J, et al.Heterozygous FOXN1 Variants Cause Low TRECs and Severe T Cell Lymphopenia, Revealing a Crucial Role of FOXN1 in Supporting Early Thymopoiesis[J].Am J Hum Genet, 2019, 105:549-561.
    [2] Adriani M, Martinez-Mir A, Fusco F, et al.Ancestral founder mutation of the nude (FOXN1) gene in congenital severe combined immunodeficiency associated with alopecia in southern Italy population[J].Ann Hum Genet, 2004, 68:265-268.
    [3] Auricchio L, Adriani M, Frank J, et al.Nail dystrophy associated with a heterozygous mutation of the nude/SCID human FOXN1(WHN) gene[J].Arch Dermatol, 2005, 141:647-648.
    [4] Du Q, Huynh LK, Coskun F, et al.FOXN1 compound heterozygous mutations cause selective thymic hypoplasia in humans[J].J Clin Invest, 2019, 129:4724-4738.
    [5] Giardino G, Sharapova SO, Ciznar P, et al.Expanding the Nude SCID/CID Phenotype Associated with FOXN1 Homozygous, Compound Heterozygous, or Heterozygous Mutations[J].J Clin Immunol, 2021, 41:756-768.
    [6] Flanagan SP.'Nude', a new hairless gene with pleiotropic effects in the mouse[J].Genet Res, 1966, 8:295-309.
    [7] Nehls M, Pfeifer D, Schorpp M, et al.New member of the winged-helix protein family disrupted in mouse and rat nude mutations[J].Nature, 1994, 372:103-107.
    [8] Pignata C, Fiore M, Guzzetta V, et al.Congenital Alopecia and nail dystrophy associated with severe functional T-cell immunodeficiency in two sibs[J].Am J Med Genet, 1996, 65:167-170.
    [9] Markert ML, Marques JG, Neven B, et al.First use of thymus transplantation therapy for FOXN1 deficiency (nude/SCID):a report of 2 cases[J].Blood, 2011, 117:688-696.
    [10] Firtina S, Cipe F, Ng YY, et al.A Novel FOXN1 Variant Is Identified in Two Siblings with Nude Severe Combined Immunodeficiency[J].J Clin Immunol, 2019, 39:144-147.
    [11] Chou J, Massaad MJ, Wakim RH, et al.A novel mutation in FOXN1 resulting in SCID:a case report and literature review[J].Clin Immunol, 2014, 155:30-32.
    [12] Albuquerque AS, Marques JG, Silva SL, et al.Human FOXN1-deficiency is associated with alphabeta double-negative and FoxP3+T-cell expansions that are distinctly modulated upon thymic transplantation[J].PLoS One, 2012, 7:e37042.
    [13] Radha RDA, Panday NN, Naushad SM.FOXN1 Italian founder mutation in Indian family:Implications in prenatal diagnosis[J].Gene, 2017, 627:222-225.
    [14] Albar R, Mahdi M, Alkeraithe F, et al.Epstein-Barr virus associated with high-grade B-cell lymphoma in nude severe combined immunodeficiency[J].BMJ Case Rep, 2019, 12, e227715.
    [15] Tangye SG, Al-Herz W, Bousfiha A, et al.Human Inborn Errors of Immunity:2019 Update on the Classification from the International Union of Immunological Societies Expert Committee[J].Journal of Clinical Immunology, 2020, 40:24-64.
    [16] Schorpp M, Hofmann M, Dear TN, et al.Characterization of mouse and human nude genes[J].Immunogenetics, 1997, 46:509-515.
    [17] Zuklys S, Handel A, Zhanybekova S, et al.Foxn1 regulates key target genes essential for T cell development in postnatal thymic epithelial cells[J].NATURE IMMUNOLOGY, 2016, 17:1206.
    [18] Schuddekopf K, Schorpp M, Boehm T.The whn transcription factor encoded by the nude locus contains an evolutionarily conserved and functionally indispensable activation domain[J].Proc Natl Acad Sci U S A, 1996, 93:9661-9664.
    [19] Vigliano I, Gorrese M, Fusco A, et al.FOXN1 mutation abrogates prenatal T-cell development in humans[J].J Med Genet, 2011, 48:413-416.
    [20] Vaidya HJ, Briones L A, Blackburn CC.FOXN1 in thymus organogenesis and development[J].Eur J Immunol, 2016, 46:1826-1837.
    [21] Nowell CS, Bredenkamp N, Tetelin S, et al.Foxn1 regulates lineage progression in cortical and medullary thymic epithelial cells but is dispensable for medullary sublineage divergence[J].PLoS Genet, 2011, 7:e1002348.
    [22] Chen L, Xiao S, Manley NR.Foxn1 is required to maintain the postnatal thymic microenvironment in a dosage-sensitive manner[J].BLOOD, 2009, 113:567-574.
    [23] Cheng L, Guo J, Sun L, et al.Postnatal tissue-specific disruption of transcription factor FoxN1 triggers acute thymic atrophy[J].J Biol Chem, 2010, 285:5836-5847.
    [24] Larsen BM, Cowan JE, Wang Y, et al.Identification of an Intronic Regulatory Element Necessary for Tissue-Specific Expression of Foxn1 in Thymic Epithelial Cells[J].The Journal of Immunology, 2019, 203:686-695.
    [25] Markert ML, Alexieff MJ, Li J, et al.Complete DiGeorge syndrome:development of rash, lymphadenopathy, and oligoclonal T cells in 5 cases[J].J Allergy Clin Immunol, 2004, 113:734-741.
    [26] Zampieri M, Ciccarone F, Calabrese R, et al.Reconfiguration of DNA methylation in aging[J].Mech Ageing Dev, 2015, 151:60-70.
    [27] Pignata C, Gaetaniello L, Masci AM, et al.Human equivalent of the mouse Nude/SCID phenotype:long-term evaluation of immunologic reconstitution after bone marrow transplantation[J].Blood, 2001, 97:880-885.
    • 相关文章
    • 施引文献
  • 资源附件(0)
  • 加载中
WeChat 点击查看大图
计量
  • 文章访问数:  10
  • HTML全文浏览量:  0
  • PDF下载量:  2
  • 被引次数: 0
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

目录

    /

    返回文章
    返回
    友情链接: 国家卫生健康委员会 北京协和医院 中国医学科学院 学术不端检测系统 国际知识资源总库 中国知网 术语在线 中国全科医学
    地址：北京市东城区帅府园1号 北京协和医院老楼7号楼
    3层302室 《协和医学杂志》编辑部
    电话：010-69154261/4262
    E - mail：medj@pumch.cn
    mjpumch@126.com
    期刊网站版权所有：《协和医学杂志》编辑部
    京ICP备 11002662

    本系统由 北京仁和汇智信息技术有限公司 开发    百度统计

    x 关闭 永久关闭

    【通知】尊敬的读者、作者及编者：因特殊原因，本站自2022.9.30至10.24日期间实施6—24点开放，其他时段访问受限，给您带来不便敬请谅解！10.25日恢复如常。