Research on expanded carrier screening for monogenic diseases
Chang Jiazhen, Qi Qingwei, Zhou Xiya, et al
(Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China)
Abstract: 【Abstract】 Objective To explore the clinical significance of expanded carrier screening (ECS) for monogenic diseases. Through a prospective cohort study of couples in the preconception period and early pregnancy, the application value of ECS in identifying high-risk couples and potentially affected individuals was evaluated. Method A total of 3 001 patients who sought ECS of monogenic diseases at the Department of Obstetrics and Gynecology, Peking Union Medical College Hospital from August 2022 to August 2023 by prospective cohort study approach. The study employed three methods—next-generation sequencing, long-range polymerase chain reaction (LR-PCR) combined with agarose gel electrophoresis, and polymerase chain reaction (PCR) combined with capillary electrophoresis to screen 223 pathogenic genes, including 197 autosomal recessive genes and 26 X-linked genes. Result Among all 3 001 subjects who participated in the ECS, a total of 1 612 individuals carried at least one pathogenic variant. In the overall population, the combined carrier rate of 197 autosomal recessive gene was 53.45% (1 604/3 001),and the combined carrier rate of 26 X-linked genes was 0.58% (9/1 547). The detection rate of high-risk couples among all the subjects was 2.48% (36/1 454), including the detection rate of 1.93% (28/1 454) for high-risk couples with autosomal recessive genes and 0.62% (9/1 454) for high-risk couples with X-linked genes. Meanwhile, in carriers of autosomal recessive genetic variants, this project unexpectedly identified 5 potentially affected individuals with homozygous or compound heterozygous variants. Additionally, among carriers of X-linked genetic variants, 7 potentially affected individuals were discovered. Conclusion ECS can not only provide support of the reproductive choice and reproductive autonomy for 2.48% of high-risk couples, but also has the opportunity to detect potentially affected individuals, and conduct conscious disease progression monitoring for patients with late-onset or only mild phenotypes.
2025, Vol. 13 
