[Analysis and clinical application of preimplantation genetic testing for monogenic disorders in a case with Spinal muscular atrophy "2+0" genotype].

OBJECTIVE:To explore the clinical application of preimplantation genetic testing for monogenic disorders (PGT-M) in an unique case with Spinal muscular atrophy (SMA) type 2+0. METHODS:A special SMA family presented at the Third Affiliated Hospital of Guangzhou Medical University on October 19, 2020 was selected as the study subject. Multiple ligation-dependent probe amplification (MLPA) and molecular tagging linkage analysis were carried out to identify the SMN1 genotype of the couple and their fetus. Subsequently, next-generation sequencing (NGS), molecular tagging linkage analysis, and chromosomal microarray analysis were employed to determine the haplotypes and validate the result of PGT-M on the 11 embryos derived for the couple. RESULTS:The female partner was identified as a carrier of the rare SMN1[2+0] variant, and prenatal diagnosis confirmed the fetus to be affected by SMA. Ultimately, PGT-M has successfully selected four embryos free from the pathogenic SMN1 variants and X chromosome deletion. CONCLUSION:PGT-M can effectively prevent the transmission of rare genetic variants such as the SMA 2+0 subtype in the families. Above finding has provided guidance for genetic counseling and family planning for the couple.