Custom exome panel revealed new mutations in MAPK14 and novel mutation in RUNX2 gene in patients with PCOS

Abstract Polycystic ovary syndrome (PCOS) is the most common endocrinopathy and is both phenotypically and genotypically heterogeneous. A large number of genetic variants have been found in different genes, so far. Based on the literature, we identified 7 genes and aimed to find new causative variants in these genes. We created a targeted PCOS panel including major genes in the steroidogenezis, WNT, MAPK, and TGFβ pathways and analyzed whole-exome sequencing results. We compared the minor allele frequency (MAF) values of different variants with our results and calculated deleterious scores of newly found variants using various web-based prediction tools and ACMG pathogenicity criteria. We found a novel missense mutation (p.Thr355Ile) in the RUNX2 gene in one patient and heterozygous mutations in the MAPK14 gene (c.306_5delT and c.*8G > T) in another patient with PCOS. Five novel pathogenic moderate (PM2) intronic variants in 4 different genes in total were introduced for the first time. We also decoded 7 genes in patients with PCOS in our cohort. Two more candidate genes (MAPK14 and RUNX2) may be related to PCOS.