Single Nucleotide Variants in A Family of Monozygotic Twins Discordant for the Phenotype Congenital Megaureter: A Genomic Analysis

Introduction: Congenital megaureter constitutes the second most frequent cause of hydronephrosis in children. There is still much debate on what extent environmental or genetic factors are involved in the pathogenesis of congenital megaureter. Objectives: This study aimed at investigating a pair of monozygotic twins discordant for the expression of bilateral congenital megaureter using the whole exome sequencing technique. Methods: Peripheral blood DNA was extracted and then sequenced using the whole exome technique from a pair of twins discordant for the presence of bilateral congenital refluxing unobstructed megaureter, his parents and a set of 11 non-related individuals with confirmed diagnosis of congenital megaureter. The DNA of the set of 11 non-related individuals was pooled in three groups. The monozygotic twins and their parents had DNA samples sequenced separately. Sanger validation was performed after data was filtered. Results: In the proband were identified 256 candidate genes, including TBX3, GATA6, DHH, LDB3, and HNF1, which are expressed in the urinary tract during the embryonic period. After Sanger validation, the SNVs found in the genes TBX3, GATA6, DHH and LDB3 were not confirmed in the proband. The SNV chr17:36104650 in the HNF1b gene was confirmed in the proband, his twin brother and the mother, however was not found in the pool of 11 non-related individuals with congenital megaureter. Conclusion: Due to the possible complex causative network of genetic variations and the challenges regarding the use of the whole exome sequencing technique we could not unequivocally associate the genetic variations identified in this study with the development of the congenital megaureter.