De novo 9q gain in an infant with tetralogy of Fallot with absent pulmonary valve: Patient report and review of congenital heart disease in 9q duplication syndrome.
De novo 9q gain in an infant with tetralogy of Fallot with absent pulmonary valve: Patient report and review of congenital heart disease in 9q duplication syndrome.
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DOI：
10.1002/ajmg.a.37296
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发表时间：
2015-12
期刊：
影响因子：
--
通讯作者：
Wambach JA
中科院分区：
文献类型：
--
作者：
Amarillo IE;O'Connor S;Lee CK;Willing M;Wambach JA
基因组破坏、表观遗传机制改变和环境因素导致先天性心脏缺陷（CHD）的异质性。近年来，染色体微阵列分析（CMA）在冠心病患者中发现了大量拷贝数变异（CNV）。因此，被这些CNVs破坏的基因是冠心病的优秀候选基因。在冠心病患者中已经发现了9q （9q+）的微重复，然而，关键基因位点仍未确定。在这里，我们讨论了一个法洛四联症婴儿，肺动脉瓣缺失，胎儿积水，通过CMA检测到9q34.2-q34.3的3.76 Mb从头开始连续增加，并通过核型和FISH研究证实。这个重复的间隔破坏了内含子1上的RXRA（类维生素a X受体α； omim# 180245）。我们还回顾了先前报道的9q （9q+）重复综合征患者的冠心病发现。这是首次报道RXRA与冠心病9q重复有关，为了解法洛四联症、冠心病和与9q微重复综合征相关的疾病的遗传病因提供了额外的数据。本报告还强调了CMA在复杂冠心病患者和家属的临床诊断和遗传咨询中的意义。
Genomic disruptions, altered epigenetic mechanisms, and environmental factors contribute to the heterogeneity of congenital heart defects (CHD). In recent years, chromosomal microarray analysis (CMA) has led to the identification of numerous copy number variations (CNV) in patients with CHD. Genes disrupted by and within these CNVs thus represent excellent candidate genes for CHD. Microduplications of 9q (9q+) have been described in patients with CHD, however, the critical gene locus remains undetermined. Here we discuss an infant with tetralogy of Fallot with absent pulmonary valve, fetal hydrops, and a 3.76 Mb de novo contiguous gain of 9q34.2-q34.3 detected by CMA, and confirmed by karyotype and FISH studies. This duplicated interval disrupted RXRA (retinoid X receptor alpha; OMIM #180245) at intron 1. We also review CHD findings among previously reported patients with 9q (9q+) duplication syndrome. This is the first report implicating RXRA in CHD with 9q duplication, providing additional data in understanding the genetic etiology of tetralogy of Fallot, CHD, and disorders linked to 9q microduplication syndrome. This report also highlights the significance of CMA in the clinical diagnosis and genetic counseling of patients and families with complex CHD.
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影响因子：
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