[Clinical implementation of monogenic disease expanded carrier screening during pregnancy]

Objective: To explore the clinical value of expanded carrier screening (ECS) for monogenic diseases in Chinese pregnant individuals. Methods: The clinical data of pregnant individuals with ECS for 334 single-gene recessive (AR or X-linked) diseases (434 pregnant woman and 315 spouses) at West China Second University Hospital of Sichuan University from May 2021 to February 2024 were retrospectively collected, including the general information, gestational age, carrier rate, detection of pathogenic/likely pathogenic (P/LP) variation with Human Gene Mutation Database (HGMD), and detection rate of at-risk couple (ARC). The diagnostic gestational weeks for ARC with concurrent screening and sequential screening mode were compared. Results: This study included 749 individuals (434 females and 315 males) with a median (Q₁, Q₃) age of 31 (28, 34) years. The carrier rate for carrying at least one P/LP variant was 65.6% (491/749). When only the P/LP variation included in HGMD was reported, detection rate of ARC was 8.3% (26/315). The actual detection rate of ARC (including P/LP variation in HGMD and not in HGMD) increased to 9.5 % (30/315). A total of 86 genes overlapped with the T3 screening genes recommended by American College of Medical Genetics and Genomics (ACMG-T3), and the detection rate of ARC was 7.0% (22/315). Compared with ACMG-T3, 334 gene screening packages covered an additional 248 genes, and the detection rate of ARC was 2.5% (8/315). The gestational age of ARC at prenatal diagnosis with concurrent screening was significantly earlier than that of sequential screening [(19.7±3.3) weeks vs (22.2±2.2) weeks, P=0.049]. Conclusion: Concurrent screening for monogenic disease carriers of multiple diseases during pregnancy will evidently advance the timing of diagnosis.