上海交通大学学报（医学版）

上海交通大学学报（医学版）

• 论著（临床研究） • 上一篇    下一篇

主动脉瓣上狭窄患者的弹力蛋白基因突变筛查

刘洋，徐丽娟，孙锟   

  1. 上海交通大学 医学院附属新华医院小儿心脏中心， 上海 200092
  • 出版日期:2016-02-28 发布日期:2016-03-29
  • 通讯作者: 孙锟, 电子信箱: drsunkun@xinhuamed.com。
  • 作者简介:刘洋(1990—)， 女， 硕士生; 电子信箱: liuyang20092008@126.com。
  • 基金资助:

    上海市卫计委重要疾病联合攻关项目（2013ZYJB0016）

Elastin gene mutation screening for patients with supravalvular aortic stenosis

LIU Yang, XU Li-juan, SUN Kun   

  1. Department of Pediatric Cardiovascular, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
  • Online:2016-02-28 Published:2016-03-29
  • Supported by:

    Joint Project of Shanghai Municipal Health Planning Commission, 2013ZYJB0016

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摘要：

目的 对综合征型和单纯型主动脉瓣上狭窄(SVAS)患者，进行弹力蛋白基因的突变筛查，分析综合征型患者心血管疾病表型差异性的原因及单纯型患者发病的遗传学基础。方法 收集8例威廉姆斯综合征(WS)患者，6例单纯型SVAS患者。采用MLPA技术进行微缺失检测，并应用PCR技术扩增弹力蛋白基因的全部外显子序列。对所有扩增片段均进行测序，将测序结果与GenBank中的弹力蛋白基因序列通过BLAST程序比对以检出可能存在的突变。结果 8例综合征型SVAS患者均有位于7q11.23区域内的杂合性缺失，长度1.04～1.61 Mb；未在单纯型SVAS患者中检测到微缺失。共检测到7个单核苷酸多态性（SNPs）位点，其中5个位于内含子区并且不涉及剪切位点;另外2个位于外显子：01号患者的第5号外显子有一突变c.212 C>T，07号患者的第25号外显子有一同义突变c.1674G>A。结论 WS患者心血管畸形表型差异性的原因及单纯型SVAS患者发病的遗传学基础，是一个复杂而又亟需解决的难题，尚需更广泛的基因筛查。

关键词: 威廉姆斯综合征, 主动脉瓣上狭窄, 弹力蛋白基因, 基因突变筛查

Abstract:

Objective To screen the elastin gene (ELN) mutations of patients with Williams syndrome (WS) or isolated supravalvular aortic stenosis (SVAS) and analyze the causes of cardiovascular variability among patients with WS and the genetic causes of the isolated SVAS. Methods Eight patients with WS and six patients with isolated SVAS were enrolled. Multiplex ligation-dependent probe amplification (MLPA) was adopted to detect the microdeletion. PCR was applied to amplify all exons of ELN gene. Direct forward and reverse sequencing was performed for all amplified fragments. The results of sequencing were compared with the sequence of elastin in GenBank by the BLAST program and possible mutations were screened. Results The microdeletion in 7q11.23 region was present in all eight patients with WS and absent in all patients with isolated SVAS and the deletion size was 1.04-1.61Mb. Among seven detected SNPs, five of them located in the intron region without involving splice-site, while another two SNPs located in exon region. The mutation c.212 C>T was detected in No. 5 exon of No.01 patient and a synonymous mutation c.1674G>A was identified in No. 25 exon of No.07 patient. Conclusion The causes of cardiovascular variability of patients with WS and the genetic causes of the isolated SVAS are complicated and need more extensive gene screening.

Key words: Williams syndrome, supravalvular aortic stenosis, elastin gene, gene mutation screening