Delivering effective genome sequencing in pediatric care: From research in the 100,000 Genomes Project to routine clinical practice

Abstract

Purpose Genome sequencing (GS) is increasingly used to investigate rare conditions, primarily in children. The 100,000 Genomes Project (100KG) evaluated GS ahead of implementation in the English National Health Service. In 2020, the National Health Service Genomic Medicine Service (GMS) became the first public health care system to offer GS in routine clinical care. We investigate how learning from 100KG informed GMS service delivery. Methods We compare GS outcomes in children tested at a large pediatric hospital via GMS ( n = 501) and 100KG research ( n = 1759). Results GMS diagnostic yield (29%) was higher than that in 100KG (22%) ( P < .0016). Median age at testing was 8 years in 100KG and 6 in the GMS ( P < .05). In 100KG, the diagnostic yield was <10% for 15 indications, none of which are included in GMS testing. 100KG data showed little benefit to application of >3 panels. Use of fewer but larger GMS panels resulted in a significantly higher number of genes tested per patient: median 2801 vs 1373 in 100KG ( P