Abstract

Background and Aims MIRAGE syndrome is an autosomal-dominant genetic disease primarily caused by a de novo mutation in the gene SAMD9 gene. This study is aimed at investigating the pathogenesis of MIRAGE syndrome through a Chinese case exhibiting intrauterine growth retardation and renal hypoplasia. Methods We performed clinical exome sequencing to identify the pathogenic loci in the family. Further functional studies were conducted to understand the impact of the identified mutation. Results We identified a de novo mutation in SAMD9 that causes MIRAGE syndrome: c.2423A>G p.(Tyr808Cys). This mutation was associated with a novel phenotypic combination of intrauterine growth retardation and renal hypoplasia in a fetus. In vitro functional experiments demonstrated that the SAMD9 mutation reduced its levels of mRNA and protein. Conclusion This study expands the pathogenic mutation spectrum of MIRAGE syndrome and provides new insights into its pathogenic mechanism. The identified mutation in SAMD9 provides a potential target for understanding and treating this complex disease.