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

Objective: The aim of this study was to develop a common targeted massively parallelsequencing platform for the noninvasive prenatal diagnosis (NIPD) of multiple X-linked diseases.Method: The custom capture probe was designed to target the 33 genes and recombination hotspots. We tested the carrier mother and male proband pair of six 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 two maternal haplotypes constructed using the common custom-designed platform.Results: The targeted sequencing of the maternal, proband, and fetus genomic DNAs and maternal plasma DNAs resulted in uniform coverage across the target region. Three to five 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 six families obtained from haplotype dosage analysis of maternal plasma sequencing data were predicted correctly.Conclusions: A single platform that covers multiple diseases may prevent the need for disease-specific probes for the NIPD of each disorder. Thus, this approach may provide a practical advantage for the clinical implementation of NIPD of X-linked diseases.