Identifying Molecular Aetiology of Syndromic and Non syndromic Renal Disorders using Exome Analysis

Abstract

Aim: Renal disorders (RDs) are heterogeneous in nature with different ages of onset ranging from in-utero to adults that arise as independent disease and also as syndromes. RDs are of both heritable and acquired type. The aim of this study was to utilize Next Generation Sequencing to identify the molecular basis of syndromic and non syndromic RDs for management and preventative counselling.Methods: In the present study cases of RDs which were identified as a solitary health issue and those which had renal disease as part of syndromic features were offered exome analysis by Next Generation Sequencing (NGS) followed by a specific gene panel evaluation after informed consent. Results: In our study twenty cases were evaluated by NGS based panel tests, a genetic variant was identified in 95% (19/20) of the cases which could be correlated with the renal phenotype. Based on the American College of Medical Genetics and Genomics (ACMG) guidelines 89% (17/19) of the cases were reported with a Pathogenic or likely pathogenic variant and 10% (2/19) with a Variant of uncertain significance. As expected 8/9 cases with features of polycystic Kidney disease and all eleven cases with syndromic RD had a variant which correlated with phenotype.Discussion & Conclusion: NGS enables molecular diagnosis of RD without subjecting patients to invasive tests like renal biopsy as early as the fetal stage. The management and prevention of disease in the family through appropriate genetic counseling is an added advantage.