Combined Carrier Screening and Prenatal Diagnosis for Spinal Muscular Atrophy, Thalassemia and Hereditary Deafness in 2873 Chinese Pregnant Women

Purpose To investigate the clinical significance of combined carrier screening and prenatal diagnosis for SMA, thalassemia and hereditary deafness. Methods There were 2873 pregnant women from Wenzhou Central Hospital in Wenzhou city Zhejiang Province, China, between February 2020 and January 2022 accepted carrier screening. Genomic DNA was extracted from saliva of the screened group. SMN1 exon 7 and/or 8 mutations were detected by real-time quantitative PCR; results were confirmed by multiplex ligation-dependent probe amplification. α- and β-globin gene mutations and hereditary deafness gene mutations were detected using PCR and flow-through hybridization techniques. DNA-based prenatal diagnosis was performed on amniotic fluid when parents both carried at least one gene mutation of the three diseases. Prenatal diagnosis was performed for 22 at-risk fetuses. Results Among 2873 pregnant women, 419 carried at least one allele associated with the three diseases (14.6%, 419/2873); 70 (2.4%) of these carried SMA alleles, 245 (8.5%) thalassemia genes, and 127 (4.4%) deafness genes. The positive rate of combined carrier screening was higher than that of a single gene test (SMA, 6.1X higher 14.6%/2.4%; thalassemia, 1.7X higher, 14.6%/8.5%; hereditary deafness, 3.3X higher 14.6%/4.4%). After detailed genetic counseling, 350 paternal partners (84%, 350/419) were tested for corresponding mutations. Three couples were SMA carriers, 14 couples were thalassemia carriers, and 5 couples were hereditary deafness gene carriers. All 22 couples underwent prenatal diagnosis; At last, 1 fetus confirmed with SMA, two with α-­thalassemia major and one with hereditary deafness. Conclusion Combined carrier screening for these three genetic diseases improves screening efficiency, increases the positive detection rate and reduces economic expenditure. We recommend a combined antenatal screening program to prevent SMA, thalassemia major and hereditary deafness at birth.