Abstract
Schaaf-Yang Syndrome (SYS) is a genetic disorder caused by truncating pathogenic variants in the paternal allele of the maternally imprinted, paternally expressed gene MAGEL2 and is characterized by genital hypoplasia, neonatal hypotonia, developmental delay, intellectual disability, autism spectrum disorder (ASD), and other features. In this study, eleven SYS patients from three families were enrolled and comprehensive clinical features were gathered regarding each family. Whole-exome sequencing (WES) was performed for the definitive molecular diagnosis of the disease. Identified variants were validated using Sanger sequencing. Three couples underwent PGT for monogenic diseases (PGT-M) and/or a prenatal diagnosis. Haplotype analysis was performed to deduce the embryo's genotype by using the short tandem repeats (STRs) identified in each sample. The prenatal diagnosis results showed that the fetus in each case did not carry pathogenic variants, and all the babies of the three families were born at full term and were healthy. We also performed a review of SYS cases. In addition to the 11 patients in our study, a total of 127 SYS patients were included in 11 papers. We summarized all variant sites and clinical symptoms thus far, and conducted a genotype-phenotype correlation analysis. Our results also indicated that the variation in phenotypic severity may depend on the specific location of the truncating variant, suggestive of a genotype-phenotype association.