A De Novo Mutation (c.2423A>G) in

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.