Clinical utility of expanded carrier screening in the preconception and prenatal population: A Chinese cohort study

• Published in: Clinica chimica acta 2025-01, Vol.565, p.120017, Article 120017
• Main Authors: Xu, Yan, Li, Ming, Hua, Renyi, Han, Xu, Wu, Yi, Chen, Yiyao, Zhao, Xinrong, Gao, Li, Li, Niu, Wang, Jian, Wang, Yanlin, Li, Shuyuan
• Format: Article
• Language: English
• Subjects: Adult; At-risk couples; China - epidemiology; Chinese population; Cohort Studies; East Asian People - genetics; Expanded carrier screening; Female; Genetic Carrier Screening - methods; Genetic Testing; Humans; Male; Preconception Care; Pregnancy; Pregnancy outcome; Prenatal Diagnosis
• ISSN: 0009-8981; 1873-3492; 1873-3492
• DOI: 10.1016/j.cca.2024.120017

•Largest Chinese cohort study using a moderate-size ECS panel.•High carrier frequency and at-risk couple rate identified.•ECS significantly influences reproductive decisions in at-risk couples.•ECS proves beneficial for both healthy individuals and those with a family history. To evaluate the clinical utility of expanded carrier screening (ECS) in Chinese preconception and prenatal populations, focusing on carrier frequency and the impact on at-risk couples (ARCs). Data from 6,298 Chinese individuals from 4,420 families who underwent a 149-gene ECS panel at a single center were analyzed. The prevalence of positive carriers and ARCs was determined, with follow-up on reproductive decisions and pregnancy outcomes for ARCs. Of the individuals screened, 2,673 (42.4 %) were carriers of at least one pathogenic or likely pathogenic variant, and 98 (2.22 %) ARCs were identified. GJB2-related deafness and Duchenne muscular dystrophy were the most common autosomal recessive (AR) and X-linked disorders. Screening the top 11 (gene carrier rate [GCR] ≥ 1/100), 22 (GCR ≥ 1/200), and 41 (GCR ≥ 1/331) AR genes could identify 53.5 %, 67.9 %, and 81.3 % of variants, respectively. The corresponding ratios for identified ARCs were 90.4 %, 94.0 %, and 100 %. Follow-up data from 80 ARCs indicated that 75.0 % (60/80) took significant action based on the ECS results. Additionally, four families (3.5 %, 4/115) were identified at risk for a second disease unrelated to their initial family monogenic history. This study, representing the largest cohort of a moderate-sized ECS panel test in the Chinese population, demonstrates the clinical utility of ECS in both healthy individuals and those with a family history of monogenic disorders. The data obtained provide valuable insights for developing a Chinese-specific ECS panel. Tailored approaches are critical for wider adoption and successful routine application of ECS.