ESPN 50th Annual Meeting

ESPN 2017


 
EXOME SEQUENCING FOR THE IDENTIFICATION OF CANDIDATE GENETIC VARIANTS IN RENAL HYPODYSPLASIA PEDIATRIC PATIENTS
SUSANNA NEGRISOLO 1 ANDREA CARRARO 1 GIULIA FREGONESE 2 DAVIDE MENEGHESSO 2 GERMANA LONGO 2 PIERGIORGIO GAMBA 4 GIORGIO VALLE 3 LUISA MURER 1

1- LABORATORY OF IMMUNOPATHOLOGY AND MOLECULAR BIOLOGY OF THE KIDNEY, WOMEN’S AND CHILDREN’S HEALTH DEPARTMENT, UNIVERSITY OF PADUA, PADUA, ITALY
2- UNIVERSITY HOSPITAL OF PADOVA, PEDIATRIC NEPHROLOGY, DIALYSIS AND TRANSPLANT UNIT, DEPARTMENT OF WOMEN’S AND CHILDREN’S HEALTH, PADUA, ITALY
3- CRIBI BIOTECHNOLOGY CENTRE, UNIVERSITY OF PADUA, PADUA, ITALY
4- UNIVERSITY OF PADOVA, PEDIATRIC SURGERY, WOMEN’S AND CHILDREN’S HEALTH DEPARTMENT, PADUA, ITALY
 
Introduction:

Non-syndromic renal hypodysplasia (RHD: OMIM #610805) is a severe congenital kidney anomaly which is a defect in the number and/or normal differentiation of nephronic units leading to kidney function impairment. RHD accounts for 20-25% of the end stage renal failures causes in children. Although 20 renal developmental genes were associated to RHD, the majority of patients remains without a genetic diagnosis. This study aims to identify new disease-causing mutations in RHD patients using Whole Exome Sequencing (WES).

Material and methods:

WES (80X average coverage) was performed with Ion Proton System in the DNA of 20 children with sporadic non-syndromic bilateral RHD, with or without associated upper urinary tract malformations. In 12/20 cases, it was possible to sequence also healthy relatives as control. WES data analysis was done using “QueryOr” variant prioritization platform (http://queryor.cribi.unipd.it/).

Results:

Our data analysis highlighted candidate variants in 60% of patients. Four were new mutations, confirmed by Sanger sequencing, in RHD genes (SIX2, SALL1, SLIT2, ROBO2) . The other variants were identified both in genes known to be associated to different renal disorder (eg. NPHS2), and as well in genes that are not  associated to renal malformations. In 8 patients none candidate variations were up to now identified.

Conclusions:

The data obtained underline a larger allelic and locus heterogeneity involved in the RHD determination. These findings suggest that a RHD diagnostic panel must comprised all syndromic and non–syndromic CAKUT genes but also renal cystic diseases genes.