Clinical application of preimplantation genetic testing for pathogenic microdeletion and microduplication based on an effective and convenient sequencing platform.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.