[en] Ranging from aplastic uterus (including Mayer–Rokitansky–Küster–Hauser syndrome) to incomplete septate uterus, uterine malformations as a group are relatively frequent in the general population. Specific causes remain largely unknown. Recurrent copy number variants are found in up to 14% of girls with Müllerian aplasia, and only a few genes have garnered strong evidence of causality, mainly in syndromic presentations. Although most occurrences ostensibly seem sporadic, familial recurrences have been observed, strongly indicating genetic factors. The aim of this thesis was to identify novel genes and pathways involved in congenital uterine anomalies. To increase the chance to identify strong genetic contributors, we selected families with recurrence of uterine and kidney malformations for genetic analyses by whole exome sequencing. Nine families were collected throughout the study. Exome sequencing analyses uncovered likely causative variations in the gene GREB1L for four of these families. In a fifth family, the candidate gene NR6A1 was selected for further functional validation. Its role in renal development and development of the genital tract was investigated in zebrafish. Both genes were sequenced in a cohort of individuals with MRKH syndrome, identifying additional heterozygous variants. Following these results, we discuss some pathways possibly involved in congenital uterine anomalies.
