Evaluating the Utility of a New Pathogenicity Predictor for Pediatric Cardiomyopathy

IF 3.3 2区医学 Q2 GENETICS & HEREDITY

Human Mutation Pub Date : 2023-10-27 DOI:10.1155/2023/8892833

Alyssa L. Rippert, Sarah Trackman, Danielle Burstein, J. William Gaynor, Heather Griffis, Christine Seymour, Rebecca Ahrens-Nicklas

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引用次数: 0

Abstract

Pediatric cardiomyopathy (CM) has significant childhood morbidity and mortality which is caused by both genetic and environmental factors. Previous research has focused on identifying genetic variants in pediatric CM for diagnostic purposes, but not for risk stratification. The current study was modeled after previous work which showed an association between CardioBoost-classified disease-causing variants and an increased risk for severe clinical outcomes in adults with CM to assess if the same association is true in pediatric CM. This was a retrospective, single-center cohort study that evaluated outcomes in pediatric CM patients who were evaluated by the Children’s Hospital of Philadelphia (CHOP). CardioBoost (CB) scores were generated for these patients, and scores were categorized as ≤0.1, 0.1-0.9, and ≥0.9. Composite endpoint was freedom from a major adverse cardiac event (MACE). 104 patients were included in the final analysis. 32 (31%) had DCM, 45 (43%) had HCM, and 27 (26%) had other CM. There was no significant association between CB score and clinical outcome in pediatric CM patients. Overall, this study highlights the continued deficits in variant interpretation for pediatric CM. We recommend using caution when applying this tool to stratify clinical outcomes in the pediatric population.

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评估一种新的儿童心肌病致病性预测因子的效用

小儿心肌病(CM)是一种由遗传和环境因素共同引起的发病率和死亡率高的疾病。以前的研究主要集中在确定儿童CM的遗传变异以用于诊断目的，而不是用于风险分层。目前的研究是在先前的研究基础上进行的，该研究显示cardioboost分类的致病变异与成人CM患者严重临床结果的风险增加之间存在关联，以评估儿童CM是否也存在相同的关联。这是一项回顾性、单中心队列研究，评估了由费城儿童医院(CHOP)评估的儿童CM患者的预后。对这些患者进行CardioBoost (CB)评分，评分分为≤0.1、0.1-0.9和≥0.9。复合终点为无主要不良心脏事件(MACE)。104例患者纳入最终分析。DCM 32例(31%)，HCM 45例(43%)，其他CM 27例(26%)。小儿CM患者CB评分与临床转归无显著相关性。总的来说，这项研究强调了儿童CM的变体解释的持续缺陷。我们建议在应用该工具对儿科人群的临床结果进行分层时谨慎使用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Human Mutation 医学-遗传学

CiteScore

8.40

自引率

5.10%

发文量

190

审稿时长

2 months

期刊介绍： Human Mutation is a peer-reviewed journal that offers publication of original Research Articles, Methods, Mutation Updates, Reviews, Database Articles, Rapid Communications, and Letters on broad aspects of mutation research in humans. Reports of novel DNA variations and their phenotypic consequences, reports of SNPs demonstrated as valuable for genomic analysis, descriptions of new molecular detection methods, and novel approaches to clinical diagnosis are welcomed. Novel reports of gene organization at the genomic level, reported in the context of mutation investigation, may be considered. The journal provides a unique forum for the exchange of ideas, methods, and applications of interest to molecular, human, and medical geneticists in academic, industrial, and clinical research settings worldwide.