全外显子组测序在八名中国孤立性法洛四联症患儿中发现新突变。
Whole exome sequencing identifies novel mutation in eight Chinese children with isolated tetralogy of Fallot.
作者信息
Liu Lin, Wang Hong-Dan, Cui Cun-Ying, Qin Yun-Yun, Fan Tai-Bing, Peng Bang-Tian, Zhang Lian-Zhong, Wang Cheng-Zeng
机构信息
Department of Cardiovascular Ultrasound, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou 450003, China.
Institute of Medical Genetics, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou 450003, China.
出版信息
Oncotarget. 2017 Oct 31;8(63):106976-106988. doi: 10.18632/oncotarget.22202. eCollection 2017 Dec 5.
BACKGROUND
Tetralogy of Fallot is the most common cyanotic congenital heart disease. However, its pathogenesis remains to be clarified. The purpose of this study was to identify the genetic variants in Tetralogy of Fallot by whole exome sequencing.
METHODS
Whole exome sequencing was performed among eight small families with Tetralogy of Fallot. Differential single nucleotide polymorphisms and small InDels were found by alignment within families and between families and then were verified by Sanger sequencing. Tetralogy of Fallot-related genes were determined by analysis using Gene Ontology /pathway, Online Mendelian Inheritance in Man, PubMed and other databases.
RESULTS
A total of sixteen differential single nucleotide polymorphisms loci and eight differential small InDels were discovered. The sixteen differential single nucleotide polymorphisms loci were located on Chr 1, 2, 4, 5, 11, 12, 15, 22 and X. Among the sixteen single nucleotide polymorphisms loci, six has not been reported. The eight differential small InDels were located on Chr 2, 4, 9, 12, 17, 19 and X, whereas of the eight differential small InDels, two has not been reported. Analysis using Gene Ontology /pathway, Online Mendelian Inheritance in Man, PubMed and other databases revealed that , , , , and were associated with Tetralogy of Fallot.
CONCLUSIONS
Our findings identify , , , , and mutations as underlying genetic causes of isolated tetralogy of Fallot.
背景
法洛四联症是最常见的青紫型先天性心脏病。然而，其发病机制仍有待阐明。本研究的目的是通过全外显子组测序鉴定法洛四联症中的基因变异。
方法
对8个患有法洛四联症的小家庭进行全外显子组测序。通过家系内和家系间比对发现差异单核苷酸多态性和小插入缺失，然后通过桑格测序进行验证。使用基因本体论/通路、《人类孟德尔遗传》、PubMed和其他数据库进行分析来确定法洛四联症相关基因。
结果
共发现16个差异单核苷酸多态性位点和8个差异小插入缺失。这16个差异单核苷酸多态性位点位于1、2、4、5、11、12、15、22号染色体和X染色体上。在这16个单核苷酸多态性位点中，有6个尚未见报道。8个差异小插入缺失位于2、4、9、12、17、19号染色体和X染色体上，而在这8个差异小插入缺失中，有2个尚未见报道。使用基因本体论/通路、《人类孟德尔遗传》、PubMed和其他数据库进行分析显示，[此处原文缺失具体基因名称]与法洛四联症相关。
结论
我们的研究结果确定[此处原文缺失具体基因名称]突变是孤立性法洛四联症的潜在遗传病因。
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