The Analysis Of Expanded Carrier Screening For Monogenic Disorders In 5903 Individuals Of Childbearing Age In Jiangxi Province

Objective: The objective of this study was to determine the carrier frequency and variant spectrum of common genetic disorders in Jiangxi population,to provide data to support the clinical application of expanded carrier screening,and to provide genetic counseling and fertility guidance for at-risk couples(ARCs).Methods: An ECS test,which covers 147 genes implicated in 155 recessive(autosomal or X-linked)disorders,was routinely offered to women considering pregnancy or with an ongoing pregnancy in Jiangxi Provincial Maternal and Child Health Hospital from March 2020 to December 2022.Sequential screening was recommended for partners of women with a positive carrier status to assess reproductive risk.Additional options such as preimplantation or prenatal genetic diagnosis were offered to ARCs,who are defined as follows: both couples carrying a pathogenic or likely pathogenic(P or LP)variant of the same autosomal recessive gene,or the female carrying a P or LP variant of an X-linked gene.The reproductive decision and pregnancy outcome were surveyed for all.Results: A total of 5903 participants,representing 4281 women and 811 couples,were recruited.Overall,2207 individuals(37.39%)were found to be carriers for at least one of the 155 disorders.A total of 138 disorders were detected,of which 11 were with carrier rates ≥1%.The most common disorders found were α-thalassemia,GJB2-associated hearing loss and Wilson Disease.A total of 910 P or LP variants were identified in the study,and the top four variants were HBA1/HBA2:-α3.7,GJB2: c.235 del C,SMN1: EX7 DEL,GALC: c.1901T>C.Among the couples tested,44 ARCs were identified.After genetic counseling,88.5%(23/26)of the ARCs who were already pregnant underwent prenatal diagnosis,and eight of them bearing an affected fetus decided to terminate the pregnancy.50%(9/18)of the ARCs before pregnancy pursued preimplantation genetic testing for monogenic defects(PGT-M).Conclusion: 1.37.39% of the participants carry at least one P or LP variant.2.The most common disorders found in Jiangxi population is α-thalassemia.3.Monogenic recessive disorders and the variant spectrum have racial and regional differences.4.Expanded carrier screening can guide reproductive decisions,improve pregnancy management,and reduce birth defects.