Saliva Sample-Based Non-Invasive Carrier Screening for Spinal Muscular Atrophy, Hereditary Hearing Loss, and Thalassemia in 13,926 Women of Reproductive Age From South Zhejiang.

BACKGROUND

Although spinal muscular atrophy (SMA), hereditary hearing loss (HL), and thalassemia are common monogenic genetic diseases, the carrier frequencies and variant spectrums of these diseases show regional differences, even within China. Their carrier frequencies and variant spectrums in Southern Zhejiang, China are unclear.

METHODS

Saliva was collected for carrier screening and amniotic fluid, villi, and peripheral blood were collected for prenatal diagnosis. Real-time quantitative polymerase chain reaction (PCR) and multiplex ligation-dependent probe amplification (MLPA) were used to detect the copy number of SMN1 exon 7. PCR coupled with flow-through hybridization, MLPA, and Sanger sequencing were used to detect common genes for HL and thalassemia.

RESULTS

Common variants were detected in 15.14% (2109/13926) of the 13,926 women of reproductive age from South Zhejiang who participated in this study. The carrier frequencies of SMA, HL, and thalassemia were 2.11% (294/13926), 4.87% (678/13926), and 8.82% (1228/13926), respectively. In total, 56.47% (1117/1978) of husbands were successfully recalled. The total number of at-risk couples was 111 (111/13926, 0.80%). Further, 47 families underwent prenatal diagnosis. A total of 13 (13/13926; 0.93‰) affected pregnancies were identified.

CONCLUSION

Our findings confirm that SMA, HL, and thalassemia are highly prevalent in Southern Zhejiang, with some regional specificity, as compared with recent large population-based surveys in China. Further, a rapid saliva sample-based non-invasive screening method was established, and its feasibility was demonstrated.