Shanshen Enas, Rosenberg Janine, Van Bergen Andrew H
Advocate Children's Heart Institute, Advocate Children's Hospital, 4440 West 95th Street, Oak Lawn, IL, 60453, USA.
ACL Laboratory, Rosemont, IL, USA.
Pediatr Cardiol. 2018 Jan;39(1):148-159. doi: 10.1007/s00246-017-1741-3. Epub 2017 Oct 9.
While the majority of patients have isolated heart disease, congenital heart disease (CHD) may be associated with other congenital anomalies or syndromes. Our institution utilizes chromosomal microarray (CMA) to identify chromosomal abnormalities, specifically copy number variations (CNVs). While CNVs have been associated with CHD, their direct impact on cardiac development remains unclear. This study sought to identify potential novel CHD candidate genes by comparing CNVs present in our institution's CHD population with those already recognized in the literature. A list of candidate genes was compiled from recent medical literature that utilized CMA. Records from neonatal cases at our institution over 10 years were reviewed. Genes identified from CMAs were compared with those reported in the literature and cross-referenced with the Online Mendelian Inheritance in Man catalog. We identified 375 CNVs reported in patients with CHD. At our institution between 2005 and 2015, 307 neonates with CHD had CMA. Of these, 77 patients (25%) had CNVs containing 832 unique candidate genes. 49 patients (16%) had isolated CHD with 353 candidate genes expressed within the CNVs, many of which were previously reported. However, there were 16 unique candidate genes identified that have been expressed with heart structure of the mouse knock-out models. Our findings demonstrate a high incidence of abnormal genes identified by CMA in CHD patients, including many CNVs of "unknown clinical significance". We conclude that a portion of these CNVs (including 16 genes expressed in the heart of the mouse knock-out models) could be candidate genes involved in CHD pathogenesis.
虽然大多数患者患有孤立性心脏病，但先天性心脏病（CHD）可能与其他先天性异常或综合征有关。我们机构利用染色体微阵列（CMA）来识别染色体异常，特别是拷贝数变异（CNV）。虽然CNV与CHD有关，但其对心脏发育的直接影响仍不清楚。本研究旨在通过比较我们机构CHD患者群体中存在的CNV与文献中已确认的CNV，来识别潜在的新型CHD候选基因。从最近利用CMA的医学文献中编制了一份候选基因清单。回顾了我们机构10多年来新生儿病例的记录。将从CMA中识别出的基因与文献中报道的基因进行比较，并与《人类孟德尔遗传在线》目录进行交叉参考。我们在CHD患者中识别出375个CNV。在我们机构2005年至2015年期间，307例患有CHD的新生儿接受了CMA检测。其中，77例患者（25%）的CNV包含832个独特的候选基因。49例患者（16%）患有孤立性CHD，其CNV中有353个候选基因表达，其中许多基因先前已有报道。然而，有16个独特的候选基因被识别出在小鼠基因敲除模型的心脏结构中表达。我们的研究结果表明，CMA在CHD患者中识别出异常基因的发生率很高，包括许多“临床意义不明”的CNV。我们得出结论，这些CNV中的一部分（包括在小鼠基因敲除模型心脏中表达的16个基因）可能是参与CHD发病机制的候选基因。
