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.
摘要：
Schaaf-Yang综合征（SYS）是一种遗传性疾病，由母系印迹的父系等位基因中的致病变异体截断引起，父系表达基因MAGEL2，以生殖器发育不全为特征，新生儿低张力,发育迟缓,智力残疾,自闭症谱系障碍（ASD），和其他功能。在这项研究中,纳入了来自三个家庭的11例SYS患者，并收集了每个家庭的综合临床特征。进行全外显子组测序（WES）以确定该疾病的分子诊断。使用Sanger测序验证鉴定的变体。三对夫妇接受了PGT单基因疾病（PGT-M）和/或产前诊断。通过使用每个样品中鉴定的短串联重复序列（STR）进行单倍型分析以推断胚胎的基因型。产前诊断结果显示,每例胎儿均未携带致病变异体,这三个家庭的所有婴儿都是足月出生的，都很健康。我们还对SYS案例进行了审查。除了我们研究中的11名患者，共127例SYS患者被纳入11篇论文.我们总结了迄今为止所有的变异部位和临床症状，进行基因型-表型相关分析。我们的结果还表明，表型严重程度的变化可能取决于截短变体的具体位置，提示基因型-表型关联。
