Abstract：Objective To observe the feasibility of maternal free fetal DNA detection in screening for fetal de novo mutations or paternal genetic diseases.Methods We selected 27 pregnant women(30-32 weeks gestation, or viviparous history of chondrodysplasia and fatal dwarfism) in the First Hospital of Shanxi Medical University from January to December 2017. The participants were 20-35 year old. 2 mL amniotic fluid was collected by ultrasound amniocentesis at 30-32 weeks of gestation for DNA Sanger sequencing and 20 mL peripheral blood for free fetal DNA mutation detection. We analyzed the fragmentation products, quality control, gene mutation and mutation sources of free fetal DNA.Results The concentration of DNA fragments in 27 maternal free fetuses(3%) ranged from 132.5 to 158 bp, which accorded with the peak distribution characteristics of DNA fragments in chondrodysplasia and lethal dwarfism. When the concentration of DNA in maternal free fetuses was 10%, 6%, 3%, 1 % and 0.5%, the peak distribution of DNA fragments ranged from 260 to 272 bp, and the quality control level of DNA documents met the Proton standard. When DNA concentration was 10%, 6% and 3%, 6 cases of gene mutation were detected by NGS sequencing, including 4 cases of chondrodysplasia and 2 cases of fatal dwarfism. The results were consistent with the results of DNA Sanger sequencing mutation. In 4 cases of chondrodysplasia, the mutation peak at c.1138 locus was significantly higher than that at other loci. The fetus carried c.1 138 > A mutation gene, and the mutation originated from the fetus. The mutation peak of c.1138(Chr4 1806119) locus in 2 lethal dwarfism samples was less than 0.1%. The mutation originated from the father gene.Conclusion When the concentration of free fetal DNA is more than 3%, the detection of maternal free fetal DNA has a high level of quality control and accuracy in screening gene mutations or paternal inheritance of fetal chondrodysplasia and fatal dwarfism, which can be analogized to prenatal diagnosis of other types of de novo mutations or paternal genetic diseases.
冯琳懿. 母体游离胎儿DNA检测在筛查胎儿新发突变或父源遗传疾病的应用[J]. 中国生育健康杂志, 2021, 32(4): 337-342.
FENG Linyi. Application of maternal free fetal DNA detection in screening for fetal mutations or paternal genetic diseases. Chinese Journal of Reproductive Health, 2021, 32(4): 337-342.
