Clinical application of expanded carrier screening based on next-generation sequencing in the Chinese population

Expanded carrier screening (ECS) enables proactive identification of at-risk couples (ARCs) and individuals, facilitating informed reproductive decision-making through genetic counseling. This study evaluates the clinical utility of ECS among the population in Anhui Province, China, where its implementation remains understudied. Retrospectively analysis of genetic testing results assessed the carrier frequencies for targeted diseases, identified prevalent pathogenic genes and variants, and ARCs detection rate alongside associated reproductive choices and pregnancy outcomes.

In this single-center retrospective study (June 2020-October 2023), 2,530 reproductive-aged individuals (486 couples; 1,558 individuals) underwent next-generation sequencing (NGS)-based ECS using a customized panel targeting 152 recessive monogenic disorders. Carrier rates, pathogenic variants, ARC detection, and subsequent reproductive outcomes were analyzed.

Overall, 38.50% (974/2,530) of participants carried ≥ 1 pathogenic/likely pathogenic (P/LP) variant. The most prevalent autosomal recessive (AR) disorders included DFNB4 (3.08%), DFNB1A (2.81%), Wilson disease (2.57%), Krabbe disease (2.37%), and phenylketonuria (2.13%). Duchenne muscular dystrophy (DMD, 0.28%) was the most common X-linked (XL) disorder. Twenty ARCs (4.12%, 20/486) were identified, including sixteen pregnant couples. Among these, 56.25% (9/16) opted for invasive prenatal diagnosis, confirming eight unaffected fetuses with healthy live births and one twin pregnancy requiring selective termination of an affected fetus. Five pregnant ARCs declined prenatal diagnosis, four of whom delivered healthy infants, while one pregnancy was terminated due to structural anomalies. Of three non-pregnant ARCs, two pursued preimplantation genetic testing for monogenic disorders (PGT-M), resulting in one healthy birth.

Our study demonstrated that the ECS for reproductive-age individuals can identify couples and individuals at risk of conceiving a child with a recessive genetic disorder and support reproductive choices through the provision of genetic counseling to reduce the likelihood of offspring with congenital anomalies.