The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; Shanghai Key Laboratory of Embryo Original Diseases, Shanghai 200030, China.
The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; Shanghai Key Laboratory of Embryo Original Diseases, Shanghai 200030, China; Institute of Birth Defects and Rare Diseases, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Clin Chim Acta. 2025 Jan 15;565:120017. doi: 10.1016/j.cca.2024.120017. Epub 2024 Oct 24.
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.
评估扩展携带者筛查（ECS）在中国孕前和产前人群中的临床应用价值，重点关注携带者频率和对高危夫妇（ARCs）的影响。
对在单一中心接受 149 基因 ECS 面板检测的 4420 个家庭的 6298 名中国个体的数据进行分析。确定阳性携带者和 ARC 的流行率，并对 ARC 的生殖决策和妊娠结局进行随访。
在接受筛查的个体中，有 2673 人（42.4%）至少携带一种致病性或可能致病性变异，发现 98 个 ARC（2.22%）。GJB2 相关耳聋和杜氏肌营养不良症是最常见的常染色体隐性（AR）和 X 连锁疾病。筛查前 11 个（基因携带者率[GCR]≥1/100）、22 个（GCR≥1/200）和 41 个（GCR≥1/331）AR 基因，分别可识别 53.5%、67.9%和 81.3%的变异，相应的 ARC 识别率分别为 90.4%、94.0%和 100%。80 个 ARC 的随访数据显示，根据 ECS 结果，75.0%（60/80）采取了重大行动。此外，有 4 个家庭（3.5%，4/115）发现存在与初始家族单基因病史无关的第二种疾病风险。
本研究代表了中国人群中中等规模 ECS 面板检测最大队列，证明了 ECS 在健康个体和有单基因疾病家族史个体中的临床应用价值。获得的数据为制定中国特定的 ECS 面板提供了有价值的见解。个体化方法对于 ECS 的广泛采用和成功常规应用至关重要。
