The application of whole-exome sequencing in the early diagnosis of rare genetic diseases in children: a study from Southeastern China.

IF 2.1 3区 医学 Q2 PEDIATRICS Frontiers in Pediatrics Pub Date : 2024-10-08 eCollection Date: 2024-01-01 DOI:10.3389/fped.2024.1448895
Guihua Lai, Qiying Gu, Zhiyong Lai, Haijun Chen, Junkun Chen, Jungao Huang
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Abstract

Background: Genetic diseases exhibit significant clinical and genetic diversity, leading to a complex and challenging diagnostic process. Exploiting novel approaches is imperative for the molecular diagnosis of genetic diseases. In this study, we utilized whole-exome sequencing (WES) to facilitate early diagnosis in patients suspected of genetic disorders.

Methods: This retrospective analysis included 144 patients diagnosed by singleton-WES Trio-WES between January 2021 and December 2023. We investigated the relevance of diagnosis rates with age, clinical presentation, and sample type.

Results: Among the 144 patients, 61 were diagnosed, yielding an overall diagnostic rate of 42.36%, with Trio-WES demonstrating a significantly higher diagnostic rate of 51.43% (36/70) compared to singleton-WES at 33.78% (25/74) (p < 0.05). Global developmental delay had a diagnosis rate of 67.39%, significantly higher than muscular hypotonia at 30.43% (p < 0.01) among different clinical phenotypic groups. Autosomal dominant disorders accounted for 70.49% (43/61) of positive cases, with autosomal abnormalities being fivefold more prevalent than sex chromosome abnormalities. Notably, sex chromosome abnormalities were more prevalent in males (80%, 8/10). Furthermore, 80.56% (29/36) of pathogenic variants were identified as de novo mutations through Trio-WES.

Conclusions: These findings highlight the effectiveness of WES in identifying genetic variants, and elucidating the molecular basis of genetic diseases, ultimately enabling early diagnosis in affected children.

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全外显子组测序在儿童罕见遗传病早期诊断中的应用:一项来自中国东南部的研究。
背景:遗传性疾病在临床和遗传方面表现出显著的多样性,导致诊断过程复杂且具有挑战性。利用新方法对遗传病进行分子诊断势在必行。在这项研究中,我们利用全外显子组测序(WES)来帮助早期诊断疑似遗传疾病患者:这项回顾性分析纳入了 2021 年 1 月至 2023 年 12 月期间通过单基因组-全外显子测序-三基因组测序确诊的 144 例患者。我们研究了诊断率与年龄、临床表现和样本类型的相关性:在 144 名患者中,61 人确诊,总诊断率为 42.36%,与单WES 的 33.78%(25/74)相比,Trio-WES 的诊断率明显更高,为 51.43%(36/70)(p p 通过 Trio-WES发现的新突变):这些研究结果凸显了 WES 在识别基因变异和阐明遗传疾病分子基础方面的有效性,最终实现了对患儿的早期诊断。
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来源期刊
Frontiers in Pediatrics
Frontiers in Pediatrics Medicine-Pediatrics, Perinatology and Child Health
CiteScore
3.60
自引率
7.70%
发文量
2132
审稿时长
14 weeks
期刊介绍: Frontiers in Pediatrics (Impact Factor 2.33) publishes rigorously peer-reviewed research broadly across the field, from basic to clinical research that meets ongoing challenges in pediatric patient care and child health. Field Chief Editors Arjan Te Pas at Leiden University and Michael L. Moritz at the Children''s Hospital of Pittsburgh are supported by an outstanding Editorial Board of international experts. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide. Frontiers in Pediatrics also features Research Topics, Frontiers special theme-focused issues managed by Guest Associate Editors, addressing important areas in pediatrics. In this fashion, Frontiers serves as an outlet to publish the broadest aspects of pediatrics in both basic and clinical research, including high-quality reviews, case reports, editorials and commentaries related to all aspects of pediatrics.
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