A meta-analysis of diagnostic yield and clinical utility of genome and exome sequencing in pediatric rare and undiagnosed genetic diseases

IF 6.6 1区医学 Q1 GENETICS & HEREDITY

Genetics in Medicine Pub Date : 2025-02-25 DOI:10.1016/j.gim.2025.101398

Rajshree Pandey , Noemi Fluetsch Brennan , Kalliopi Trachana , Sarah Katsandres , Olaf Bodamer , John Belmont , David L. Veenstra , Siyang Peng

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引用次数: 0

Abstract

Purpose

To systematically evaluate the diagnostic yield and clinical utility of genome sequencing (GS) and exome sequencing (ES; genome-wide sequencing [GWS]) in pediatric patients with rare and undiagnosed genetic diseases.

Methods

We conducted a meta-analysis of studies published between 2011 and 2023. To address study heterogeneity, comparative analyses included within-cohort studies using random-effects models.

Results

We identified 108 studies including 24,631 probands with diverse clinical indications. The pooled diagnostic yield among within-cohort studies (N = 13) for GWS was 34.2% (95% CI: 27.6-41.5; I²: 86%) vs 18.1% (95% CI: 13.1-24.6; I²: 89%) for non-GWS, with 2.4-times odds of diagnosis (95% CI: 1.40-4.04; P < .05). The pooled diagnostic yield among within-cohort studies (N = 3) for GS was 30.6% (95% CI: 18.6-45.9; I²: 79%) vs 23.2% (95% CI: 18.5-28.7; I²: 58%) for ES, with 1.7-times the odds of diagnosis (95% CI: 0.94-2.92; P = .13). In first-line testing, the diagnostic yield tended to be higher for GS than for ES across clinical subgroups. The pooled clinical utility among patients with a positive diagnosis was 58.7% (95% CI: 47.3-69.2; I²: 81%) for GS and 54.5% (95% CI: 40.7-67.6; I ²: 87%) for ES.

Conclusion

GS appears to have a higher diagnostic yield than ES, with similar clinical utility per positive diagnosis.

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来源期刊

Genetics in Medicine 医学-遗传学

CiteScore

15.20

自引率

6.80%

发文量

857

审稿时长

1.3 weeks

期刊介绍： Genetics in Medicine (GIM) is the official journal of the American College of Medical Genetics and Genomics. The journal''s mission is to enhance the knowledge, understanding, and practice of medical genetics and genomics through publications in clinical and laboratory genetics and genomics, including ethical, legal, and social issues as well as public health. GIM encourages research that combats racism, includes diverse populations and is written by authors from diverse and underrepresented backgrounds.