Department of Child Health Care, Children's Hospital of Fudan University, Shanghai 201102, China.
Pediatric Department, Suining Central Hospital, Suining 629000, China.
Genes (Basel). 2022 Jun 2;13(6):1010. doi: 10.3390/genes13061010.
Autism spectrum disorder (ASD) is an early-onset neurodevelopmental disorder in which genetics play a major role. Molecular diagnosis may lead to a more accurate prognosis, improved clinical management, and potential treatment of the condition. Both copy number variations (CNVs) and single nucleotide variations (SNVs) have been reported to contribute to the genetic etiology of ASD. The effectiveness and validity of clinical targeted panel sequencing (CTPS) designed to analyze both CNVs and SNVs can be evaluated in different ASD cohorts. CTPS was performed on 573 patients with the diagnosis of ASD. Medical records of positive CTPS cases were further reviewed and analyzed. Additional medical examinations were performed for a group of selective cases. Positive molecular findings were confirmed by orthogonal methods. The overall positive rate was 19.16% (109/569) in our cohort. About 13.89% (79/569) and 4.40% (25/569) of cases had SNVs only and CNVs only findings, respectively, while 0.9% (5/569) of cases had both SNV and CNV findings. For cases with SNVs findings, the gene has the greatest number of reportable variants, followed by gene . Patients with variants share common and specific clinical characteristics. We found a child with compound heterozygous variants had an enlarged vestibular aqueduct syndrome and autistic phenotype. Our results showed that CTPS is an effective molecular diagnostic tool for ASD. Thorough clinical and genetic evaluation of ASD can lead to more accurate diagnosis and better management of the condition.
自闭症谱系障碍（ASD）是一种早期发病的神经发育障碍，遗传在其中起着重要作用。分子诊断可能导致更准确的预后、改善临床管理和潜在的疾病治疗。拷贝数变异（CNVs）和单核苷酸变异（SNVs）都被报道与 ASD 的遗传病因有关。设计用于分析 CNVs 和 SNVs 的临床靶向panel 测序（CTPS）的有效性和有效性可以在不同的 ASD 队列中进行评估。对 573 名被诊断为 ASD 的患者进行了 CTPS。进一步审查和分析了 CTPS 阳性病例的病历。对一组选择性病例进行了额外的医学检查。通过正交方法确认阳性分子发现。在我们的队列中，总体阳性率为 19.16%（109/569）。约 13.89%（79/569）和 4.40%（25/569）的病例分别仅发现 SNVs 和 CNVs，而 0.9%（5/569）的病例同时发现 SNV 和 CNV。对于具有 SNVs 发现的病例，基因具有最多的可报告变异，其次是基因。具有变异的患者具有共同和特定的临床特征。我们发现一名患有复合杂合变异的儿童患有前庭导水管扩大综合征和自闭症表型。我们的结果表明，CTPS 是 ASD 的有效分子诊断工具。对 ASD 进行彻底的临床和遗传评估可以导致更准确的诊断和更好的疾病管理。
