Comprehensive expanded carrier screening using next-generation sequencing in Southern Chinese couples

Abstract Background Carrier screening has been an effective way to prevent severe birth defects in many countries. However, it has not been widely performed in China. In order to identify the local carrier mutation spectrum of autosomal/X-linked recessive diseases in the southeast coastal region in China, a pilot study of mutation carrier screening analysis of a 332-genes panel has been performed on 440 samples from Fujian Province. Methods An NGS-based, expanded carrier screening (ECS) panel of 332 genes implicated in 343 AR/XLR diseases in 220 couples in the Fujian region has been developed. Multidimensional data analysis on the detected SNV/Indels and CNVs, including demographics, carrier frequencies and mutation burden of the corresponding diseases has been performed. Results 511 mutations, including 43 (8.41%) CNVs, were identified in 440 samples, involving 133 genes and 123 diseases. The overall estimated incidence is 1/51. The average P/LP mutation burden per sample (MBP) was 1.16. The highest MBP was observed in Reproductive Assistance (RA)-group who had histories of second and third trimesters fetal loss/abnormalities or postnatal abnormalities. The rate of at-risk couples (ARCs) was 6.36% (n = 14), implicating seven diseases. No difference was observed in the ARCs rate between the Genetic Screening (GS)-group and RA-group. Totally 23 diseases were identified (28 genes) with accumulated carrier frequency ≥ 1/100. The recurrent mutations in GAA, GALT, CYP1B1, and MEFV showed a different mutation spectrum compared to hotspots previously reported in the Han Chinese. Conclusions Our study showed that NGS-based ECS has great potential to identify disease carrier burdens and at-risk couples in this Southeast China coastal region, Fujian province. Regional carrier screening disease priority list, instead of a general Chinese population screening gene list, should be carefully determined before the launch of an official public health decision to perform carrier screening at local hospitals in this region.