Assessment of large copy number variants in patients with apparently isolated congenital left-sided cardiac lesions reveals clinically relevant genomic events.
Assessment of large copy number variants in patients with apparently isolated congenital left-sided cardiac lesions reveals clinically relevant genomic events.
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DOI：
10.1002/ajmg.a.38309
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发表时间：
2017-08
期刊：
影响因子：
--
通讯作者：
Belmont JW
中科院分区：
文献类型：
--
作者：
Hanchard NA;Umana LA;D'Alessandro L;Azamian M;Poopola M;Morris SA;Fernbach S;Lalani SR;Towbin JA;Zender GA;Fitzgerald-Butt S;Garg V;Bowman J;Zapata G;Hernandez P;Arrington CB;Furthner D;Prakash SK;Bowles NE;McBride KL;Belmont JW
Congenital left-sided cardiac lesions (LSLs) are a significant contributor to the mortality and morbidity of congenital heart disease (CHD). Structural copy number variants (CNVs) have been implicated in LSL without extra-cardiac features; however, non-penetrance and variable expressivity have created uncertainty over the use of CNV analyses in such patients. High-density SNP microarray genotyping data was used to infer large, likely-pathogenic, autosomal CNVs in a cohort of 1,139 probands with LSL and their families. CNVs were molecularly confirmed and the medical records of individual carriers reviewed. The gene content of novel CNVs was then compared with public CNV data from CHD patients. Large CNVs (> 1 MB) were observed in 33 probands (~3%). Six of these were de novo and 14 were not observed in the only available parent sample. Associated cardiac phenotypes spanned a broad spectrum without clear predilection. Candidate CNVs were largely non-recurrent, associated with heterozygous loss of copy number, and overlapped known CHD genomic regions. Novel CNV regions were enriched for cardiac development genes, including seven that have not been previously associated with human CHD. CNV analysis can be a clinically useful and molecularly informative tool in LSLs without obvious extra-cardiac defects, and may identify a clinically-relevant genomic disorder in a small but important proportion of these individuals.
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DOI：
10.1016/j.jtcvs.2015.09.136
发表时间：
2016-04
期刊：
The Journal of thoracic and cardiovascular surgery
影响因子：
--
作者：
Kim DS;Kim JH;Burt AA;Crosslin DR;Burnham N;Kim CE;McDonald-McGinn DM;Zackai EH;Nicolson SC;Spray TL;Stanaway IB;Nickerson DA;Heagerty PJ;Hakonarson H;Gaynor JW;Jarvik GP
通讯作者：
Jarvik GP
影响因子：
1
作者：
Bachman, Kristine K.;DeWard, Stephanie J.;Madan-Khetarpal, Suneeta
通讯作者：
Madan-Khetarpal, Suneeta
影响因子：
0.3
作者：
Connor, Jessica A.;Hinton, Robert B.;Ware, Stephanie M.
通讯作者：
Ware, Stephanie M.
影响因子：
30.8
作者：
Cooper, Gregory M.;Coe, Bradley P.;Eichler, Evan E.
通讯作者：
Eichler, Evan E.
影响因子：
4.5
作者：
Kuang SQ;Guo DC;Prakash SK;McDonald ML;Johnson RJ;Wang M;Regalado ES;Russell L;Cao JM;Kwartler C;Fraivillig K;Coselli JS;Safi HJ;Estrera AL;Leal SM;LeMaire SA;Belmont JW;Milewicz DM;GenTAC Investigators
通讯作者：
GenTAC Investigators