Clinical application of preimplantation genetic testing for pathogenic microdeletion and microduplication based on an...

PGT utilizing SNP-based linkage analysis for monogenic defects associated with microdeletions/duplications has been the standard method for preventing disease inheritance. However, its high cost and time consumption limit its accessibility. This study introduces a novel platform, the GenoLab M DX gene sequencer, designed to leverage next-generation sequencing (NGS) technology, aiming to reduce costs and increase sequencing efficiency in preimplantation genetic testing (PGT) for microdeletions/duplications.

Couples with microdeletion/duplication syndromes were recruited, and GenoLab was employed to detect copy number variations (CNVs) under 4 Mb in their abnormal blastocysts, developmentally arrested embryos, and peripheral blood, assessing the diagnostic validity of GenoLab.

Blastocysts and arrested embryos from eight couples were thawed and sequenced using GenoLab. Of 69 affected blastocyst samples, 49 (71.0%) exhibited submicroscopic abnormalities, with 94% concordance to prior biopsy findings. Among 15 arrested embryo samples, 6 (40%) showed submicroscopic abnormalities, while 3 (20%) were mosaic. Additionally, 138 developmentally arrested embryos, peripheral blood, and 1 abortive tissue were analyzed, achieving diagnostic accuracy exceeding 90%. Clinically, two couples with microdeletions/duplications had embryos successfully transferred, resulting in the birth of two healthy children.

The GenoLab M DX sequencer is a reliable, rapid (< 2 weeks), and cost-effective platform suitable for CNV analysis in monogenic diseases. It offers an innovative solution for cases involving de novo pathogenic variants or when family DNA samples are unavailable, representing a significant advancement in assisted reproduction.