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探讨自闭症谱系障碍患儿队列中的基因检测请求、基因改变和临床关联。

Exploring genetic testing requests, genetic alterations and clinical associations in a cohort of children with autism spectrum disorder.

机构信息

Instituto de Biomedicina de Sevilla, Seville, Spain.

University of Seville, Seville, Spain.

出版信息

Eur Child Adolesc Psychiatry. 2024 Nov;33(11):3829-3840. doi: 10.1007/s00787-024-02413-x. Epub 2024 Apr 8.

Abstract

Several studies show great heterogeneity in the type of genetic test requested and in the clinicopathological characteristics of patients with ASD. The following study aims, firstly, to explore the factors that might influence professionals' decisions about the appropriateness of requesting genetic testing for their patients with ASD and, secondly, to determine the prevalence of genetic alterations in a representative sample of children with a diagnosis of ASD. Methods: We studied the clinical factors associated with the request for genetic testing in a sample of 440 children with ASD and the clinical factors of present genetic alterations. Even though the main guidelines recommend genetic testing all children with an ASD diagnosis, only 56% of children with an ASD diagnosis were genetically tested. The prevalence of genetic alterations was 17.5%. These alterations were more often associated with intellectual disability and dysmorphic features. There are no objective data to explicitly justify the request for genetic testing, nor are there objective data to justify requesting one genetic study versus multiple studies. Remarkably, only 28% of males were genetically tested with the recommended tests (fragile X and CMA). Children with dysmorphic features and organic comorbidities were more likely to be genetic tested than those without. Previous diagnosis of ASD (family history of ASD) and attendance at specialist services were also associated with Genetically tested Autism Spectrum Disorder GTASD. Our findings emphasize the importance of establishing algorithms to facilitate targeted genetic consultation for individuals with ASD who are likely to benefit, considering clinical phenotypes, efficiency, ethics, and benefits.

摘要

多项研究表明,对于 ASD 患者的遗传检测类型和临床病理特征存在很大的异质性。本研究旨在:首先,探讨可能影响专业人员决定是否对 ASD 患者进行基因检测的因素;其次,确定在 ASD 诊断的代表性儿童样本中遗传改变的发生率。方法:我们研究了 440 名 ASD 儿童样本中与基因检测请求相关的临床因素以及目前遗传改变的临床因素。尽管主要指南建议对所有 ASD 诊断的儿童进行基因检测,但只有 56%的 ASD 诊断的儿童进行了基因检测。遗传改变的发生率为 17.5%。这些改变更常与智力残疾和发育异常有关。没有明确的客观数据可以证明基因检测请求的合理性,也没有客观数据可以证明请求一项基因研究而不是多项研究的合理性。值得注意的是,只有 28%的男性接受了推荐的测试(脆性 X 和 CMA)进行基因检测。有发育异常和器质性合并症的儿童比没有这些特征的儿童更有可能接受基因检测。先前的 ASD 诊断(ASD 家族史)和专科服务的就诊也与 GTASD(遗传检测 ASD)相关。我们的研究结果强调了制定算法的重要性,以促进可能受益于考虑临床表型、效率、伦理和获益的个体的有针对性的遗传咨询。

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