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

Augusto C Soares Dos Santos Junior,Raony G Corrêa Do Carmo Lisboa Cardenas Cardenas,Ana C Simoes E Silva,Luiz A Cunha De Marco,Eduardo A Oliveira,Luciana B Rodrigues,Debora M De Miranda,Patricia G.P Couto

doi:10.2174/1874303x01710010011

Augusto C Soares Dos Santos Junior, Raony G Corrêa Do Carmo Lisboa Cardenas Cardenas + Show 6 more

Open Access

https://doi.org/10.2174/1874303x01710010011

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Journal: The Open Urology & Nephrology Journal	Publication Date: May 30, 2017
Citations: 1	License type: CC BY 4.0

Abstract

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.

Highlights

Congenital megaureter constitutes the second most frequent cause of hydronephrosis in children
The SNV chr17:36104650 in the HNF1b gene was confirmed in the proband, his twin brother and the mother, was not found in the pool of 11 non-related individuals with congenital megaureter
12 The Open Urology & Nephrology Journal, 2017, Volume 10 sequencing technique we could not unequivocally associate the genetic variations identified in this study with the development of the congenital megaureter

Summary

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. There is still much debate on what extent environmental, epigenetic or genetic factors are implicated in the pathogenesis of CAKUT. The current most accepted theory supports the influence of a complex interaction between environmental, epigenetic and genetic factors, suggesting that the pathogenesis of CAKUT is multifactorial [7]. Changes affecting single nucleotides could be a possible mechanism to trigger abnormal pathways, which would eventually signal to the development of the megaureter [11 - 13]. In this context, several genes have emerged as potential candidates [14]. The exons represents only about 1.5% of the genome, it is currently believed that 85% of all genetic diseases derive from modifications in this region of the genome [23, 24]

Objectives

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Conclusion