A genotype-first analysis in a cohort of Mullerian anomaly

Müllerian anomaly (M.A.) is a group of congenital anatomic abnormalities caused by aberrations of the development process of the Müllerian duct. M.A. can either be isolated or be involved in Mendelian syndromes, such as Dandy-Walker syndrome, Holt–Oram syndrome and Bardet–Biedl syndrome, which are often associated with both uterus and kidney malformations. In this study, we applied a genotype-first approach to analyze the whole-exome sequencing data of 492 patients with M.A. Six potential pathogenic variants were found in five genes previously related to female urogenital deformities ( PKD1, SON, SALL1, BMPR1B, ITGA8 ), which are partially overlapping with our patients’ phenotypes. We further identified eight incidental findings in seven genes related to Mendelian syndromes without known association with reproductive anomalies ( TEK, COL11A1, ANKRD11, LEMD3, DLG5, SPTB, BMP2 ), which represent potential phenotype expansions of these genes.