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

• Tác giả: John Belmont, Olaf Bodamer, Noemi Fluetsch Brennan, Sarah Katsandres, Rajshree Pandey, Siyang Peng, Kalliopi Trachana, David L Veenstra
• Ngôn ngữ: eng
• Thông tin xuất bản: United States : Genetics in medicine : official journal of the American College of Medical Genetics , 2025
• Bộ sưu tập: NCBI
• ID: 734952

Tóm tắt

 PURPOSE: To systematically evaluate the diagnostic yield and clinical utility of genome and exome sequencing (GS and ES
  genome-wide sequencing [GWS]) in pediatric patients with rare and undiagnosed genetic diseases. METHODS: We conducted a meta-analysis to evaluate studies published between 2011 and 2023. To address study heterogeneity, comparative analyses included within-cohort studies only using random effects models. RESULTS: We identified 108 studies including a total of 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% (13.1, 24.6
  I2: 89%) for non-GWS, with 2.4-times odds of diagnosis (1.40, 4.04
  p<
 0.05). The pooled diagnostic yield among within-cohort studies (N=3) for GS was 30.6% (18.6, 45.9
  I2: 79%) vs. 23.2% (18.5, 28.7
  I2: 58%) for ES, with 1.7-times odds of diagnosis (95% CI: 0.94, 2.92
  p=0.13). In 1st-line testing, diagnostic yield trended higher for GS vs. ES across clinical subgroups. The pooled clinical utility among patients with positive diagnoses was 58.7% (47.3, 69.2%
  I 2: 81%) for GS and 54.5% (40.7, 67.6%
  I 2: 87%) for ES. CONCLUSION: GS appears to have higher diagnostic yield than ES, with similar clinical utility per positive diagnosis.