Identification of candidate genes for congenital heart defects on proximal chromosome 8p.
Identification of candidate genes for congenital heart defects on proximal chromosome 8p.
复制标题
近端染色体 8p 上先天性心脏病候选基因的鉴定。
DOI：
10.1038/srep36133
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发表时间：
2016-11-03
影响因子：
4.6
通讯作者：
Xu R
中科院分区：
文献类型：
--
作者：
Li T;Liu C;Xu Y;Guo Q;Chen S;Sun K;Xu R
随着先进的分子细胞遗传学技术的应用，8p染色体异常患者的数量逐渐增加。8p末端缺失的个体在以前的研究中已经被广泛描述。其表现通常包括心脏畸形、发育迟缓/智力低下、颅面畸形和多种其他轻微异常。然而，一些近端缺失的患者也表现出类似的表型特征。在这里，我们描述了一名女性儿童，在8p11.23-p22有18.5-Mb缺失，包括心脏相关基因NKX2-6和NRG1。对14 3例房间隔缺损患者进行两个候选基因的突变筛查，发现两个杂合性突变NKX2-6(c.1a >； T)和nrg1(c.1652G >； A)。这些突变首次在先天性心脏病(CHD)患者中被描述。C1a >； TNKX2-6产生了一个截短45个氨基酸的蛋白质，表达水平下降，而突变对蛋白质功能没有显著影响。我们的发现提示8p21-8p12可能是8p相关性CHD的另一个关键区域，一些心脏畸形可能是由于NKX2-6单倍体不足所致。这项研究还首次将NKX2-6突变与ASD联系起来，为这种常见形式的CHD的分子基础提供了新的见解。
With the application of advanced molecular cytogenetic techniques, the number of patients identified as having abnormal chromosome 8p has increased progressively. Individuals with terminal 8p deletion have been extensively described in previous studies. The manifestations usually include cardiac anomalies, developmental delay/mental retardation, craniofacial abnormalities, and multiple other minor anomalies. However, some patients with proximal deletion also presented with similar phenotypic features. Here we describe a female child with an 18.5-Mb deletion at 8p11.23–p22 that include the cardiac-associated loci NKX2-6 and NRG1. Further mutation screening of these two candidate genes in 143 atrial septal defect patients, two heterozygous mutations NKX2-6 (c.1A > T) and NRG1 (c.1652G > A) were identified. The mutations were described for the first time in patients with congenital heart disease (CHD). The c.1A > T NKX2-6 generated a protein truncated by 45 amino acids with a decreased level of mRNA expression, whereas the NRG1 mutation had no significant effect on protein functions. Our findings suggest that 8p21-8p12 may be another critical region for 8p-associated CHD, and some cardiac malformations might be due to NKX2-6 haploinsufficiency. This study also links the NKX2-6 mutation to ASD for the first time, providing novel insight into the molecular underpinning of this common form of CHD.
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影响因子：
4.4
作者：
McInnes, Lynne A.;Ouchanov, Leonid;Manghi, Elina R.
通讯作者：
Manghi, Elina R.
影响因子：
5.2
作者：
Glancy, Mary;Barnicoat, Angela;Barber, John C. K.
通讯作者：
Barber, John C. K.
影响因子：
5
作者：
Kuramochi, Yukio;Guo, Xinxin;Sawyer, Douglas B.
通讯作者：
Sawyer, Douglas B.
DOI：
10.1152/ajpheart.1999.277.5.h2026
发表时间：
1999-11-01
影响因子：
4.8
作者：
Baliga, RR;Pimental, DR;Kelly, RA
通讯作者：
Kelly, RA
DOI：
10.1002/ajmg.b.30219
发表时间：
2005-11-05
影响因子：
2.8
作者：
Go, RCP;Perry, RT;Sweet, RA
通讯作者：
Sweet, RA