摘要
目的应用全外显子测序技术对2例癫痫患儿进行基因检测以明确诊断,探讨全外显子测序技术对癫痫的基因诊断价值。方法分别提取2例癫痫患儿(患儿1、2)及其父母的外周血DNA,采用全外显子测序技术对其进行基因检测,采用Sanger测序法对2例患儿及其父母的可疑致病基因变异进行验证。明确病因后,分别抽取2例孕妇(患儿母亲)的羊水,提取胎儿DNA,采用Sanger测序法进一步对胎儿进行产前诊断。结果患儿1 SCN2A基因存在c.4399C>G错义杂合变异,其父母该位点均为野生型,胎儿该位点也为野生型,其父母选择继续妊娠;患儿2 TBC1D24基因存在c.76G>T和c.1595C>G复合杂合变异,分别遗传自其父母,胎儿为c.76G>T杂合变异携带者,其父母选择继续妊娠。结论 TBC1D24基因c.76G>T和c.1595C>G复合杂合变异、SCN2A基因c.4399C>G杂合变异可能是癫痫患儿的致病原因,全外显子测序技术可快速、准确地对癫痫进行基因诊断。
Objective To carry out mutation analysis for diagnosis of two children with epilepsy by whole exome sequencing(WES) and explore the value of WES technology to the detection of pathogenic genes in children with epilepsy. Methods Peripheral blood DNA was extracted from two children(patient A and B) with epilepsy and their parents, WES was employed to detect potential mutations, and Sanger sequencing was applied to verify the mutations in two patients and their parents. After the etiology of the patients was determined, the amniotic fluid was extracted from their mothers to obtain DNA, of the fetus and the prenatal diagnosis of the fetus in the family was further conducted by Sanger sequencing. Results A de novo mutaion of SCN2 A c.4399 C>G was detected in patient A, showing wide type in the fetus and the parents. Compound heterozygous mutations of c.76 G>T and c.1595 C>G in TBC1 D24 gene were detected in patient B, inherited from the parents, and the fetus was a carrier of c.76 G>T. The parents of these two children chose to continue pregnancy. Conclusion The de novo mutaion of SCN2 A c.4399 C>G and compound heterozygous mutations of c.76 G>T and c.1595 C>G in TBC1 D24 gene may be the main reasons for these patients, and WES can accurately and quickly make the diagnosis of heterogeneous epilepsy.
作者
张冰
杨科
张玉薇
肖海
张倩
娄桂予
祁娜
廖世秀
ZHANG Bing;YANG Ke;ZHANG Yu-wei;XIAO Hai;ZHANG Qian;LOU Gui-yu;QI Na;LIAO Shi-xiu(Medical Genetics Institute,Henan Provincial People’s Hospital,Zhengzhou University People’s Hospital,Medical Genetics Institute of Henan Province,Zhengzhou,Henan 450003,China)
出处
《中华实用诊断与治疗杂志》
2021年第4期412-415,共4页
Journal of Chinese Practical Diagnosis and Therapy
基金
2020年河南省医学科技攻关计划(联合共建)项目(LHGJ20190594)
2018年河南省科技攻关项目(182102310551)。
