Copy Number Variants of Undetermined Significance Are Not Associated with Worse Clinical Outcomes in Hypoplastic Left Heart Syndrome.
Copy Number Variants of Undetermined Significance Are Not Associated with Worse Clinical Outcomes in Hypoplastic Left Heart Syndrome.
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DOI：
10.1016/j.jpeds.2018.07.022
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发表时间：
2018-11
期刊：
影响因子：
--
通讯作者：
Landstrom AP
中科院分区：
文献类型：
--
作者：
Dailey-Schwartz AL;Tadros HJ;Azamian MS;Lalani SR;Morris SA;Allen HD;Kim JJ;Landstrom AP
确定在患有左心发育不良综合征（HLHS）的新生儿中染色体微阵列（CMA）上观察到的意义不明的拷贝数变异（cnVUS）的患病率、谱和预后意义。确定了2008年6月至2016年12月期间在德克萨斯州儿童医院就诊的HLHS新生儿。CMA结果被提取并与从文献中收集的表面健康个体的拷贝数变异（CNVs）进行比较。结果被归类为正常，与已知的遗传性疾病或cnVUS一致。然后使用Kaplan Meier分析比较生存率。次要结局包括气管切开术、出院时饲管、心脏骤停和体外膜肺氧合（ECMO）。我们的研究纳入了105例HLHS新生儿; 70例（66.7%）CMA结果正常，9例（8.6%）与已知遗传性疾病一致，26例（24.7%）有cnVUS。26例cnVUS患者中有6例（23.0%）具有定位于健康对照人群中所见的基因组特定区域的变异。cnVUS、CMA正常或已知遗传性疾病患者的1年生存率分别为84.0%、68.3%和33.3%（P=0.003）。次要结局无显著差异，但值得注意的是，15.7%的CMA正常患者使用了ECMO，而cnVUS和异常结果患者未使用ECMO（P=0.038）。在患有HLHS的儿童中，CMA检测到的cnVUS很常见。cnVUS没有定位于基因组的特定区域，与CMA正常的儿童相比，与更差的结果无关。
To determine the prevalence, spectrum, and prognostic significance of copy number variants of undetermined significance (cnVUS) seen on chromosomal microarray (CMA) in neonates with hypoplastic left heart syndrome (HLHS). Neonates with HLHS who presented between June 2008 and December 2016 to Texas Children’s Hospital were identified. CMA results were abstracted and compared against copy number variations (CNVs) in ostensibly healthy individuals, gathered from the literature. Findings were classified as normal, consistent with a known genetic disorder, or cnVUS. Survival was then compared using Kaplan Meier analysis. Secondary outcomes included tracheostomy, feeding tube at discharge, cardiac arrest, and extracorporeal membrane oxygenation (ECMO). Our study included 105 neonates with HLHS; 70 (66.7%) had normal CMA results, 9 (8.6%) had findings consistent with known genetic disorders, and 26 (24.7%) had a cnVUS. Six of the 26 (23.0%) cnVUS patients had a variant that localized to a specific region of the genome seen among the healthy control population. One-year survival in patients with a cnVUS, normal CMA, or known genetic disorders was 84.0%, 68.3% and 33.3%, respectively (P=0.003). There was no significant difference in secondary outcomes, although notably ECMO was utilized in 15.7% of patients with normal CMA and was not used in patients with cnVUS and abnormal results (P=0.038). Among children with HLHS, cnVUSs detected on CMA are common. The cnVUSs did not localize to specific regions of the genome and were not associated with worse outcomes compared with children with a normal CMA.
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