Genetic etiologic analysis in 74 Chinese Han women with idiopathic premature ovarian insufficiency by combined molecular genetic testing

Purpose To identify the disease-causing genes of Chinese Han women with idiopathic premature ovarian insufficiency (POI). Methods Seventy-four Chinese Han women with idiopathic POI were collected to analyze the genetic etiology. Triplet repeat-primed polymerase chain reaction (TP-PCR) was performed to screen the FMR1 (CGG)n premutation, and then 60 POI-related genes were sequenced by targeted next-generation sequencing (NGS) in POI patients with normal FMR1 . Results A total of one patient (1/74) with FMR1 premutation was identified. Targeted NGS revealed that 15.07% (11/73) patients had pathogenic or likely pathogenic variants of Mendelian genes ( FOXL2 , EIF2B2 , CYP17A1 , CLPP , MCM9 , GDF9 , MSH5 , ERCC6 , POLG ). Ten novel variants in six Mendelian genes were identified, such as CLPP c.355A>C (p.I119L) and c.688A>C (p.M230L), MCM9 c.1157C>T (p.T386M) and c.1291A>G (p.M431V), GDF9 c. 238C>T (p.Q80X), MSH5 c.604G>C (p.G202R) and c.2063T>C (p.I688T), ERCC6 c.C1769C>T (p.P590L), POLG c.2832G>C (p.E944D), and c.2821A>G (p.I941V). Conclusion This study suggested targeted NGS was an efficient etiologic test for idiopathic POI patients without FMR1 premutation and enriched the variant spectrum of POI-related genes.