The feasibility study of Ion Proton semiconductor sequencing platform in the non-invasive prenatal genetic diagnosis

Abstract

Objective To evaluate the feasibility of apply Ion Proton semiconductor sequencing platform in non-invasive prenatal genetic diagnosis. Methods Totally 1 000 pregnant women with a singleton pregnancy of 12-32 weeks gestation were selected from the Third affiliated Hospital of Zhengzhou University from Jan to Dec 2013. Using noninvasive prenatal genetic diagnosis based on Ion Proton semiconductor sequencing platform to study their cffDNA. In parallel, 72 pregnant women received invasive prenatal diagnosis by traditional chromosomal analysis with amniocentesis chorionic villus sampling. Results It′s shown that 18 out of 1 000 (1.8%) pregnant women underwent the noninvasive prenatal genetic testing had a high risk for aneuploid chromosomes, including 7 cases of 21-trisomy, 4 cases of 18-trisomy, 2 cases of 13-trisomy, 4 cases of sex chromosomal abnormality, and 1 case of 15-trisomy. It demonstrated that the rate and accuracy of fetal 21-trisomy, 13-trisomy and 18-trisomy by non-invasive prenatal genetic testing were both 100% without misdiagnosis, the rate of detection for sex chromosomal abnormality was 2/2 with a false positive rate of 1/3. However, the 15-trisomy predicted by the non-invasive prenatal diagnosis in a woman was finally proved to be a false positive. Based on the results by karyotyping (55/55) as well as follow-ups (493/493), the specificity of the non-invasive prenatal diagnosis for detection of 21-trisomy, 18-trisomy and 13-trisomy was 100%. One Ion PITM chip could detect 12 to 15 samples in 1.5 h and the whole process of noninvasive detection could be completed in 1 to 1.5 days. Conclusions The non-invasive prenatal diagnosis by Ion Proton semiconductor sequencing platform could provide fast and accurate detection of fetal aneuploidy. The benchtop high-throughput sequencing platform has laid the foundation for the independent application in clinical settings for fetal aneuploidy detection. （Chin J Lab Med，2014,37：861-865） Key words: Prenatal diagnosis; Aneuploidy; Chromosome aberrations; Aneuploidy; Sequence analysis, DNA; High-throughput nucleotide sequencing; Feasibility studies