Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands.
Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands.
复制标题
DOI：
10.1038/ng.3970
复制
发表时间：
2017-11
期刊：
影响因子：
30.8
通讯作者：
Brueckner M
中科院分区：
文献类型：
--
作者：
Jin SC;Homsy J;Zaidi S;Lu Q;Morton S;DePalma SR;Zeng X;Qi H;Chang W;Sierant MC;Hung WC;Haider S;Zhang J;Knight J;Bjornson RD;Castaldi C;Tikhonoa IR;Bilguvar K;Mane SM;Sanders SJ;Mital S;Russell MW;Gaynor JW;Deanfield J;Giardini A;Porter GA Jr;Srivastava D;Lo CW;Shen Y;Watkins WS;Yandell M;Yost HJ;Tristani-Firouzi M;Newburger JW;Roberts AE;Kim R;Zhao H;Kaltman JR;Goldmuntz E;Chung WK;Seidman JG;Gelb BD;Seidman CE;Lifton RP;Brueckner M
先天性心脏病（CHD）是出生缺陷导致死亡的主要原因。对2，871名CHD先证者（包括2，645名父母-后代三人组）的单个队列进行外显子组测序，发现1.8%的罕见遗传突变，包括GDF 1中的隐性创始者突变，占Ashkenazim中重度CHD的约5%，MYH 6中的隐性基因型占Shone复合体的约11%，显性FLT 4突变占法洛四联症的2.3%。新生突变（DNM）占8%的病例，包括约3%的孤立性CHD患者和约28%的神经发育和心外先天性异常。7个基因超过了全基因组显著性阈值，12个先前与CHD无关的基因具有> 70%的疾病相关概率;推断约440个基因中的DNM有助于CHD。在先心病和自闭症的先证者中，具有破坏性DNM的基因之间存在惊人的重叠。
Congenital heart disease (CHD) is the leading cause of mortality from birth defects. Exome sequencing of a single cohort of 2,871 CHD probands including 2,645 parent-offspring trios implicated rare inherited mutations in 1.8%, including a recessive founder mutation in GDF1 accounting for ~5% of severe CHD in Ashkenazim, recessive genotypes in MYH6 accounting for ~11% of Shone complex, and dominant FLT4 mutations accounting for 2.3% of Tetralogy of Fallot. De novo mutations (DNMs) accounted for 8% of cases, including ~3% of isolated CHD patients and ~28% with both neurodevelopmental and extra-cardiac congenital anomalies. Seven genes surpassed thresholds for genome-wide significance and 12 genes not previously implicated in CHD had > 70% probability of being disease-related; DNMs in ~440 genes are inferred to contribute to CHD. There was striking overlap between genes with damaging DNMs in probands with CHD and autism.
登录
查看更多内容
影响因子：
30.8
作者：
Krumm, Niklas;Turner, Tychele N.;Baker, Carl;Vives, Laura;Mohajeri, Kiana;Witherspoon, Kali;Raja, Archana;Coe, Bradley P.;Stessman, Holly A.;He, Zong-Xiao;Leal, Suzanne M.;Bernier, Raphael;Eichler, Evan E.
通讯作者：
Eichler, Evan E.
影响因子：
64.8
作者：
Iossifov, Ivan;O'Roak, Brian J.;Sanders, Stephan J.;Ronemus, Michael;Krumm, Niklas;Levy, Dan;Stessman, Holly A.;Witherspoon, Kali T.;Vives, Laura;Patterson, Karynne E.;Smith, Joshua D.;Paeper, Bryan;Nickerson, Deborah A.;Dea, Jeanselle;Dong, Shan;Gonzalez, Luis E.;Mandell, Jeffrey D.;Mane, Shrikant M.;Murtha, Michael T.;Sullivan, Catherine A.;Walker, Michael F.;Waqar, Zainulabedin;Wei, Liping;Willsey, A. Jeremy;Yamrom, Boris;Lee, Yoon-ha;Grabowska, Ewa;Dalkic, Ertugrul;Wang, Zihua;Marks, Steven;Andrews, Peter;Leotta, Anthony;Kendall, Jude;Hakker, Inessa;Rosenbaum, Julie;Ma, Beicong;Rodgers, Linda;Troge, Jennifer;Narzisi, Giuseppe;Yoon, Seungtai;Schatz, Michael C.;Ye, Kenny;McCombie, W. Richard;Shendure, Jay;Eichler, Evan E.;State, Matthew W.;Wigler, Michael
通讯作者：
Wigler, Michael
影响因子：
20.1
作者：
Pediatric Cardiac Genomics Consortium;Gelb B;Brueckner M;Chung W;Goldmuntz E;Kaltman J;Kaski JP;Kim R;Kline J;Mercer-Rosa L;Porter G;Roberts A;Rosenberg E;Seiden H;Seidman C;Sleeper L;Tennstedt S;Kaltman J;Schramm C;Burns K;Pearson G;Rosenberg E
通讯作者：
Rosenberg E
影响因子：
0.7
作者：
Egbe A;Lee S;Ho D;Uppu S;Srivastava S
通讯作者：
Srivastava S
影响因子：
2.1
作者：
Hu, Hao;Huff, Chad D.;Moore, Barry;Flygare, Steven;Reese, Martin G.;Yandell, Mark
通讯作者：
Yandell, Mark