Objective
To investigate the role of SC genes in the pathogenesis of sporadic POI and NOA. Design: Genetic and functional study. Setting: University-based reproductive medicine center. Patient(s): A total of 1030 patients with sporadic POI and 400 patients with sporadic NOA. Intervention(s): The variations of SC genes were filtered in the in-house database of whole exome sequencing performed in 1030 patients with sporadic POI and 400 patients with sporadic NOA. The pathogenic or likely pathogenic variations following recessive inheritance mode were selected according to American College of Medical Genetics and Genomics (ACMG) guidelines and confirmed by Sanger sequencing. The pathogenic effects of the variations were verified by functional studies. Main outcome measure(s): ACMG classification and functional characteristics. Result(s): Two homozygous variations of C14ORF39 and 2 recessive variations of SYCE1 were first identified in sporadic patients with POI and NOA, respectively. Functional studies showed the C14ORF39 variations significantly accelerated the protein degradation and the variations in SYCE1 disrupted its interaction with SYCP1 or C14ORF39, both of which affected SC assembly and meiosis.