Utilizing Long-Read Sequencing for Haplotype Construction and Prevention of Autosomal Dominant Polycystic Kidney Disease Transmission in Mosaicism Family.

Abstract

This study presents a case of autosomal dominant polycystic kidney disease (ADPKD) involving a mosaic microdeletion in the PKD1 gene and explores the application of long-read sequencing technologies for haplotype construction and preimplantation genetic testing (PGT). We report on a family where the proband was clinically diagnosed with PKD and found to have a partial deletion of the PKD1 gene because of the mosaic deletion mutation of PKD1 in the mother of the proband. Utilizing Oxford Nanopore long-read sequencing, we successfully constructed the haplotype of the deleted fragment region and identified an unaffected embryo for transplantation, resulting in a successful pregnancy. The prenatal genetic diagnosis confirmed the absence of deletion abnormalities in the fetus. Our findings underscore the significance of integrating advanced genomic technologies into clinical practice for PGT in ADPKD, particularly in cases involving partial deletion of X chromosome mosaic embryo transferred or complex structural variants. This approach not only prevents the transmission of ADPKD but also demonstrates the utility of long-read sequencing in overcoming the limitations of traditional PGT methods. Further research is warranted to evaluate the broader application of long-read sequencing for other monogenic disorders and to refine these techniques for enhanced diagnostic precision and clinical outcomes.