Department of Orthopedic Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences; Beijing, 100730, China.
Beijing Key Laboratory for Genetic Research of Skeletal Deformity; Beijing, China.
JAMA Pediatr. 2023 Nov 1;177(11):1149-1157. doi: 10.1001/jamapediatrics.2023.3566.
Currently, the diagnostic yield of exome sequencing (ES) and chromosomal microarray analysis (CMA) for short stature cohorts is uncertain. Despite previous studies reporting the widespread use of ES and CMA, a definitive diagnostic yield has not been established.
To investigate the diagnostic yield of ES and CMA in short stature.
A systematic literature search was conducted using relevant keywords in 3 databases (PubMed, Embase, and Web of Science) in February 2023.
Eligible studies for meta-analysis were those that had at least 10 participants with short stature who were diagnosed using either ES or CMA and the number of diagnosed patients was reported. Of 5222 identified studies, 20 were eventually included in the study.
Two independent investigators extracted relevant information from each study, which was then synthesized using proportional meta-analysis to obtain the overall diagnostic yield of ES and CMA.
The primary outcome measure was to determine the overall diagnostic yield of ES and CMA. A subgroup meta-analysis was also performed to assess if the diagnostic yield varied depending on whether ES was used as a first-tier or last-resort test. Additionally, a meta-regression was carried out to investigate how the diagnostic yield varied over time.
Twenty studies were included, comprising 1350 patients with short stature who underwent ES and 1070 patients who completed CMA. The overall diagnostic yield of ES among the cohorts and CMA among the cohorts was found to be 27.1% (95% CI, 18.1%-37.2%) and 13.6% (95% CI, 9.2%-18.7%), respectively. No statistically significant difference was observed between the first-tier (27.8%; 95% CI, 15.7%-41.8%) and last-resort groups (25.6%; 95% CI, 13.6%-39.6%) (P = .83) or in the percentage of positively diagnosed patients over time. No statistically significant difference was observed between the first-tier (27.8%; 95% CI, 15.7%-41.8%) and last-resort groups (25.6%; 95% CI, 13.6%-39.6%) (P = .83) or in the percentage of positively diagnosed patients over time.
This systematic review and meta-analysis provides high-level evidence supporting the diagnostic efficacy of ES and CMA in patients with short stature. The findings serve as a solid reference for clinicians when making informed decisions about recommending these genetic tests.
目前，外显子组测序（ES）和染色体微阵列分析（CMA）在矮小队列中的诊断率尚不确定。尽管先前的研究报告了 ES 和 CMA 的广泛应用，但尚未确定明确的诊断率。
调查 ES 和 CMA 在矮小症中的诊断率。
2023 年 2 月，使用 3 个数据库（PubMed、Embase 和 Web of Science）中的相关关键词进行了系统的文献搜索。
进行荟萃分析的合格研究是指至少有 10 名接受 ES 或 CMA 诊断的矮小症患者的研究，并且报告了诊断患者的数量。在 5222 项确定的研究中，最终有 20 项研究被纳入研究。
两名独立的研究人员从每项研究中提取相关信息，然后使用比例荟萃分析综合这些信息，以获得 ES 和 CMA 的总体诊断率。
主要结果是确定 ES 和 CMA 的总体诊断率。还进行了亚组荟萃分析，以评估 ES 是否作为一线或最后手段测试时诊断率是否有所不同。此外，还进行了荟萃回归分析，以研究诊断率随时间的变化情况。
共纳入 20 项研究，包括 1350 名接受 ES 检查的矮小症患者和 1070 名完成 CMA 检查的患者。队列中 ES 的总体诊断率和队列中 CMA 的总体诊断率分别为 27.1%（95%CI，18.1%-37.2%）和 13.6%（95%CI，9.2%-18.7%）。第一级（27.8%；95%CI，15.7%-41.8%）和最后手段组（25.6%；95%CI，13.6%-39.6%）之间（P=0.83）或随时间推移阳性诊断患者的百分比之间未观察到统计学差异。第一级（27.8%；95%CI，15.7%-41.8%）和最后手段组（25.6%；95%CI，13.6%-39.6%）之间（P=0.83）或随时间推移阳性诊断患者的百分比之间未观察到统计学差异。
本系统评价和荟萃分析提供了高水平的证据，支持 ES 和 CMA 在矮小症患者中的诊断效果。这些发现为临床医生在决定推荐这些基因检测时提供了可靠的参考。
