中华皮肤科杂志 ›› 2019, Vol. 52 ›› Issue (7): 450-454.doi: 10.3760/cma.j.issn.0412-4030.2019.07.002

• 论著 • 上一篇    下一篇

NEMO基因镶嵌突变致男性色素失禁症一例

潘玉雪1,杨勇2,林志淼1   

  1. 1北京大学第一医院皮肤科  北京市皮肤病分子诊断重点实验室  100034；
    2中国医学科学院  北京协和医学院  皮肤病医院遗传室，南京  210042 
  • 收稿日期:2018-11-30 修回日期:2019-04-05 出版日期:2019-07-15 发布日期:2019-07-01
  • 通讯作者: 林志淼 E-mail:zhimiaolin@bjmu.edu.cn
  • 基金资助:
    国家自然科学基金（81573032）

Mosaic mutation in the NEMO gene causes incontinentia pigmenti in a male patient

Pan Yuxue1, Yang Yong2, Lin Zhimiao1   

  1. 1Department of Dermatology, Peking University First Hospital, Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing 100034, China; 2Center for Genetic Diseases, Hospital for Skin Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China
  • Received:2018-11-30 Revised:2019-04-05 Online:2019-07-15 Published:2019-07-01
  • Contact: Lin Zhimiao E-mail:zhimiaolin@bjmu.edu.cn
  • Supported by:
    National Natural Science Foundation of China （81573032）

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摘要： 【摘要】 目的 检测1个色素失禁症家系NEMO基因的突变情况。方法 收集先证者临床资料，提取先证者及其父母和200例健康对照外周血DNA。采用多重PCR扩增的方法检测先证者及其父亲外周血DNA中是否存在NEMO基因4 ~ 10号外显子杂合性缺失；PCR扩增所有血液样本NEMO基因2号外显子和3 ~ 10号外显子片段，并对其基因编码区的全部外显子及其侧翼序列进行测序。提取先证者父亲皮损石蜡组织DNA，PCR扩增NEMO基因10号外显子及其侧翼序列并测序。结果 先证者及其父亲外周血DNA中均不存在NEMO基因4 ~ 10号外显子缺失；Sanger测序发现先证者外周血NEMO基因10号外显子发生c.1236dupA杂合突变，导致氨基酸出现p.H413fs*7改变。先证者父母外周血中均不存在c.1236dupA突变，但先证者父亲皮损组织DNA中存在c.1236dupA镶嵌突变。结论 NEMO基因c.1236dupA突变可能为引起本例先证者及其父亲色素失禁症的原因。

关键词: 色素失调症, DNA突变分析, 镶嵌现象, 皮肤表现, NEMO基因

Abstract: 【Abstract】 Objective To identify mutations in the NEMO gene in a family with incontinentia pigmenti. Methods Clinical data were collected from the proband, and peripheral blood samples were obtained from the proband, her parents and 200 healthy controls. Multiplex PCR was performed to detect heterozygous deletion of exons 4 - 10 of the NEMO gene in the blood samples of the proband and her parents. Then, PCR was performed to amplify exons 2, 3 - 10 of the NEMO gene in all the blood samples, and all exons in the gene coding region and their flanking sequences were subjected to DNA sequencing. DNA was extracted from paraffin?embedded lesional tissue of the proband′s father, and PCR was performed to amplify exon 10 of the NEMO gene and its flanking sequence followed by DNA sequencing. Results The deletion of exons 4 - 10 of the NEMO gene was undetected in the peripheral blood of the proband or her father. Sanger sequencing showed that there was a heterozygous mutation c.1236dupA in exon 10 of the NEMO gene in the peripheral blood of the proband, which led to a mutation in amino acid residues（p. H413fs*7）. The c.1236dupA mutation was not found in the peripheral blood of the proband′s parents, while a mosaic mutation c.1236dupA was detected in the DNA from lesional tissues of the proband′s father. Conclusion The mutation c.1236dupA in the NEMO gene may be the underlying cause of incontinentia pigmenti in the proband and her father.

Key words: Incontinentia pigmenti, DNA mutational analysis, Mosaicism, Skin manifestations, NEMO gene

中图分类号: 

  • R758.5+5