Amplicon Resequencing Identified Parental Mosaicism for Approximately   10% of &quot;de novo&quot; SCN1A Mutations in Children with Dravet Syndrome

doi:10.1002/humu.22819

CORC > 北京大学 > 生命科学学院

	Amplicon Resequencing Identified Parental Mosaicism for Approximately 10% of "de novo" SCN1A Mutations in Children with Dravet Syndrome
	Xu, Xiaojing ; Yang, Xiaoxu ; Wu, Qixi ; Liu, Aijie ; Yang, Xiaoling ; Ye, Adam Yongxin ; Huang, August Yue ; Li, Jiarui ; Wang, Meng ; Yu, Zhe ; Wang, Sheng ; Zhang, Zhichao ; Wu, Xiru ; Wei, Liping ; Zhang, Yuehua
刊名	HUMAN MUTATION
	2015
关键词	de novo mosaic Dravet syndrome SCN1A next-generation sequencing somatic mutation SEVERE MYOCLONIC EPILEPSY AUTISM SPECTRUM DISORDERS HUMAN GENETIC-DISEASE SOMATIC MOSAICISM MISSENSE MUTATION FEBRILE SEIZURES POINT MUTATIONS DENOVO MUTATION MARFAN-SYNDROME ALPORT-SYNDROME
DOI	10.1002/humu.22819
英文摘要	The majority of children with Dravet syndrome (DS) are caused by de novo SCN1A mutations. To investigate the origin of the mutations, we developed and applied a new method that combined deep amplicon resequencing with a Bayesian model to detect and quantify allelic fractions with improved sensitivity. Of 174 SCN1A mutations in DS probands which were considered de novo by Sanger sequencing, we identified 15 cases (8.6%) of parental mosaicism. We identified another five cases of parental mosaicism that were also detectable by Sanger sequencing. Fraction of mutant alleles in the 20 cases of parental mosaicism ranged from 1.1% to 32.6%. Thirteen (65% of 20) mutations originated paternally and seven (35% of 20) maternally. Twelve (60% of 20) mosaic parents did not have any epileptic symptoms. Their mutant allelic fractions were significantly lower than those in mosaic parents with epileptic symptoms (P = 0.016). We identified mosaicism with varied allelic fractions in blood, saliva, urine, hair follicle, oral epithelium, and semen, demonstrating that postzygotic mutations could affect multiple somatic cells as well as germ cells. Our results suggest that more sensitive tools for detecting low-level mosaicism in parents of families with seemingly de novo mutations will allow for better informed genetic counseling. Published 2015 Wiley Periodicals, Inc.; Ministry of Science and Technology of China [2012CB837600]; National Natural Science Foundation of China [81171221]; Peking University Clinical Cooperation "985 Project" [PKU-2014-1-1, PKU-2013-1-06]; Beijing Municipal Science and Technology Commission [Z131100006813046]; SCI(E); PubMed; ARTICLE; weilp@mail.cbi.pku.edu.cn; zhangyhdr@126.com; 9; 861-872; 36
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/416926]
专题	生命科学学院
推荐引用方式 GB/T 7714	Xu, Xiaojing,Yang, Xiaoxu,Wu, Qixi,et al. Amplicon Resequencing Identified Parental Mosaicism for Approximately 10% of "de novo" SCN1A Mutations in Children with Dravet Syndrome[J]. HUMAN MUTATION,2015.
APA	Xu, Xiaojing.,Yang, Xiaoxu.,Wu, Qixi.,Liu, Aijie.,Yang, Xiaoling.,...&Zhang, Yuehua.(2015).Amplicon Resequencing Identified Parental Mosaicism for Approximately 10% of "de novo" SCN1A Mutations in Children with Dravet Syndrome.HUMAN MUTATION.
MLA	Xu, Xiaojing,et al."Amplicon Resequencing Identified Parental Mosaicism for Approximately 10% of "de novo" SCN1A Mutations in Children with Dravet Syndrome".HUMAN MUTATION (2015).