Identification of novel candidate gene loci and increased sex chromosome aneuploidy among infants with conotruncal heart defects.
Identification of novel candidate gene loci and increased sex chromosome aneuploidy among infants with conotruncal heart defects.
复制标题
鉴定出新的候选基因基因座和性染色体的性染色体肾上腺倍性的增加，患有伴有心脏缺陷的婴儿。
DOI：
10.1002/ajmg.a.36291
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发表时间：
2014-02
影响因子：
2
通讯作者：
Lammer, Edward J.
中科院分区：
文献类型：
--
作者：
Osoegawa, Kazutoyo;Iovannisci, David M.;Lin, Bin;Parodi, Christina;Schultz, Kathleen;Shaw, Gary M.;Lammer, Edward J.
关键词：
先天性心脏缺陷是常见的畸形，每1 000名新生儿中有4-8名患有先天性心脏缺陷。圆锥动脉干缺损是先天性心脏病的一个重要病因，占先天性心脏病总数的近20%。尽管已知环境和遗传因素都会导致圆锥干缺陷的发生，但大多数人的原因仍然未知。为了鉴定新的候选基因/位点，我们使用阵列比较基因组杂交来检测染色体微缺失/重复。从1999-2004年出生的974，579名新生儿中，我们筛选了389名出生时患有法洛四联症或d型大动脉转位的加州婴儿。我们发现，1.7%（5/288）的圆锥干缺陷的男性有性染色体非整倍体，频率增加了7倍（相对危险度= 7.0; 95%置信区间2.9-16.9）。我们确定了8个染色体微缺失/重复锥干缺陷。从这些重复和缺失中，我们发现了五个高优先级的候选基因（GATA 4，CRKL，BMPR 1A，SNAI 2和ZFHX 4）。这是首次报道性染色体非整倍体与男孩圆锥动脉干缺陷有关。这些染色体微复制/缺失提供了证据，证明GATA 4、SNAI 2和CRKL是参与流出道发育的高剂量敏感基因。拷贝数变异的全基因组筛查对于鉴定导致非综合征性常见畸形的新基因/位点是有成效的。
Congenital heart defects are common malformations, affecting 4–8 per 1,000 total births. Conotruncal defects are an important pathogenetic subset of congenital heart defects, comprising nearly 20 percent of the total. Although both environmental and genetic factors are known to contribute to the occurrence of conotruncal defects, the causes remain unknown for most. To identify novel candidate genes/loci, we used array comparative genomic hybridization to detect chromosomal microdeletions/duplications. From a population base of 974,579 total births born during 1999–2004, we screened 389 California infants born with tetralogy of Fallot or d-transposition of the great arteries. We found that 1.7% (5/288) of males with a conotruncal defect had sex chromosome aneuploidy, a seven-fold increased frequency (relative risk = 7.0; 95% confidence interval 2.9–16.9). We identified eight chromosomal microdeletions/duplications for conotruncal defects. From these duplications and deletions, we found five high priority candidate genes (GATA4, CRKL, BMPR1A, SNAI2 and ZFHX4). This is the initial report that sex chromosome aneuploidy is associated with conotruncal defects among boys. These chromosomal microduplications/deletions provide evidence that GATA4, SNAI2 and CRKL are highly dosage sensitive genes involved in outflow tract development. Genome wide screening for copy number variation can be productive for identifying novel genes/loci contributing to nonsyndromic common malformations.
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影响因子：
5.2
作者：
Morris, Joan K.;Alberman, Eva;Jacobs, Patricia
通讯作者：
Jacobs, Patricia
影响因子：
9.8
作者：
Hollox, EJ;Armour, JAL;Barber, JCK
通讯作者：
Barber, JCK
影响因子：
64.5
作者：
Merscher, S;Funke, B;Kucherlapati, R
通讯作者：
Kucherlapati, R
影响因子：
2
作者：
Hemmi, Kazunori;Ma, Dongping;Tsuchiya, Kayoko
通讯作者：
Tsuchiya, Kayoko
DOI：
10.1002/bdra.20541
发表时间：
2009-01-01
影响因子：
--
作者：
Lammer, Edward J.;Chak, Jacqueline S.;Shaw, Gary M.
通讯作者：
Shaw, Gary M.