中华皮肤科杂志 ›› 2012, Vol. 45 ›› Issue (12): 847-849.

• 论著 • 上一篇    下一篇

毛囊闭锁三联征一家系调查及致病基因突变检测

任伟萍1,2,王李云1,3,梅爱华1,2,陈岚1,2,邓云华2,陈兴平2   

  1. 1.
    2. 华中科技大学同济医学院附属同济医院
    3. 湖北省蕲春县人民医院皮肤科
  • 收稿日期:2012-01-10 修回日期:2012-03-12 出版日期:2012-12-15 发布日期:2012-11-30
  • 通讯作者: 邓云华 E-mail:yhdeng@mails.tjmu.edu.cn
  • 基金资助:

    一个FPH致病基因的鉴定;色素代谢新基因ABCB6的功能研究

Follicular occlusion triad in a family: a clinical survey and mutational analysis

  • Received:2012-01-10 Revised:2012-03-12 Online:2012-12-15 Published:2012-11-30
  • Contact: yunhua deng E-mail:yhdeng@mails.tjmu.edu.cn

PDF

54

赞

摘要：

目的 研究一个毛囊闭锁三联征家系的临床特征及其致病基因的突变类型。方法 依据确诊的毛囊闭锁三联征先证者对该家系进行现场调查，并采集外周血标本。运用PCR扩增早老素1（PSEN1）、单过性跨膜蛋白（NCSTN）和早老素增强子2 （PSENEN）的所有外显子，经测序与比对后鉴定致病基因突变位点和突变方式。结果 该家系共有3代14人，其中6人患病（男4例，女2例），符合常染色体显性遗传模式。对4例现存患者临床特征比较分析表明，患者临床表型差异显著。对3个基因的DNA测序分析发现，NCSTN基因6号外显子存在c.647A > C（p.Q216P）错义突变，且在该家系中基因型与表型呈完全共分离现象。同时检测100名健康对照，未发现该突变。检索美国国家生物技术信息中心（NCBI）网站单核苷酸多态性（SNP）数据库，未发现该突变。结论 该家系存在一个新的错义突变，即NCSTN基因6号外显子c.647A > C，这可能是该家系患者发病的分子基础。

关键词: DNA突变分析

Abstract:

Objective To observe the clinical features and to identify γ-secretase gene mutations in a Chinese family with follicular occlusion triad （FOT）. Methods Clinical evaluation was carried out in a family with FOT through field investigation. Peripheral blood samples were obtained from the family members and 100 unrelated healthy controls. DNA was extracted from the blood samples, and PCR was performed to amplify all the coding regions of PSEN1, PSENEN and NCSTN genes followed by DNA sequencing and comparative analysis. Results There were 14 members over 3 generations in this family, of whom, 6 （4 males and 2 females） were affected by FOT. FOT was inherited in an autosomal dominant manner in this family. Clinical manifestations varied greatly among the 4 surviving affected members. DNA sequencing revealed a novel missense mutation, c.647A > C（p.Q216P）, in the exon 6 of NCSTN gene in the proband, which was cosegregated perfectly with affected, but not with unaffected, members in the family. The mutation was not found in any of the unrelated controls and had not been registered in the single nucleotide polymorphism （SNP） database in NCBI. Conclusions There is a novel heterozygous missense mutation, c.647A>C in the exon 6 of NCSTN gene, which may be the molecular basis of pathogenesis of FOT in this family.