Population-based frequency of surfactant dysfunction mutations in a native Chinese cohort

Background Rare mutations in surfactant-associated genes contribute to neonatal respiratory distress syndrome. The frequency of mutations in these genes in the Chinese population is unknown. Methods We obtained blood spots from the Guangxi Neonatal Screening Center in Nanning, China that included Han ( n =443) and Zhuang ( n =313) ethnic groups. We resequenced all exons of the surfactant proteins-B ( SFTPB ), -C ( SFTPC ), and the ATP-binding cassette member A3 ( ABCA3 ) genes and compared the frequencies of 5 common and all rare variants. Results We found minor differences in the frequencies of the common variants in the Han and Zhuang cohorts. We did not find any rare mutations in SFTPB or SFTPC , but we found three ABCA3 mutations in the Han [minor allele frequency (MAF)=0.003] and 7 in the Zhuang (MAF=0.011) cohorts ( P =0.10). The ABCA3 mutations were unique to each cohort; five were novel. The collapsed carrier rate of rare ABCA3 mutations in the Han and Zhuang populations combined was 1.3%, which is significantly lower than that in the United States ( P <0.001). Conclusion The population-based frequency of mutations in ABCA3 in south China newborns is significantly lower than that in United States. The contribution of these rare ABCA3 mutations to disease burden in the south China population is still unknown.