Noninvasive prenatal diagnosis of 21-hydroxylase deficiency using target capture sequencing of maternal plasma DNA

Ma D,Wang J,Wang W,Yang H,Guo F,Cheng J,Sun Y,Zhang J,Yi X,Xu Z,Yuan Y,Wang Y,Z Xu Asan,Jiang T,Hu P,Luo C,Chen C

doi:10.1530/ey.15.8.8

Abstract

Noninvasive prenatal diagnosis of 21-hydroxylase deficiency using target capture sequencing of maternal plasma DNA

Highlights

We aimed to validate a noninvasive method using capture sequencing for prenatal diagnosis of congenital adrenal hyperplasia due to 21-Hydroxylase deficiency (21-OHD)
We showed that noninvasive prenatal testing (NIPT) of fetal 21-OHD can be accomplished by analyzing a 274.15 kb targeted region, including CYP21A2 and 1607 surrounding highly heterozygous single nucleotide polymorphism (SNP) distributed within 2 Mbp chromosome 6 region
To investigate the effect of fetal DNA fraction and sequencing depth on the accuracy of our method, we prepared a series of artificial mixtures by mixing the maternal genomic DNA (gDNA) from family F-02’s and paired fetal gDNA derived from the first pregnancy

Summary

Introduction

We aimed to validate a noninvasive method using capture sequencing for prenatal diagnosis of congenital adrenal hyperplasia due to 21-Hydroxylase deficiency (21-OHD). Results suggest the accuracy and feasibility of NIPD of 21-OHD using a small target capture region with a low threshold for fetal DNA fraction and sequence depth. We have successfully reported noninvasive prenatal diagnosis (NIPD) of fetal CYP21A2 genotype using a combination of target capture sequencing and haplotype-assisted analysis[17]. New et al reported that target capture sequencing of a 6 Mb region flanking CYP21A2, facilitated noninvasive genotype analysis of fetus in CAH using relative haplotype dosage (RHDO) analysis[18]. These studies demonstrated that target capture sequencing can be used in noninvasive prenatal diagnosis of fetal CAH. Our approach suggests an affordable strategy for clinical application of NIPT of monogenic diseases such as 21-OHD

Objectives

Methods

Results

Conclusion