Development of a common platform for the noninvasive prenatal diagnosis of X-linked diseases

The aim of this study was to develop a common targeted massively parallel sequencing platform for the noninvasive prenatal diagnosis (NIPD) of multiple X-linked diseases.

The custom capture probe was designed to target 33 genes and recombination hotspots. We tested the carrier mother and male proband pair of 6 families. Plasma DNA of the pregnant carrier mother was collected at different gestational weeks and sequenced. The fetal genotype of each family was determined by estimating the imbalance between the 2 maternal haplotypes constructed using a common custom-designed platform.

The targeted sequencing of the maternal, proband, and fetal genomic DNAs and maternal plasma DNAs resulted in uniform coverage across the target region. Three to 5 recombination points were observed in each sample. However, these recombination points did not affect the haplotype dosage analysis for fetal genotype prediction. Consequently, all fetal genotypes in the 6 families obtained from haplotype dosage analysis of maternal plasma sequencing data were predicted correctly.

Since a single platform that covers multiple diseases may prevent the need for disease-specific probes for the NIPD of individual disorders, this approach may provide a practical advantage for clinically implementing the NIPD of X-linked diseases.