Characterization of Novel Truncated Variants Identified From Indian Autosomal Dominant Polycystic Kidney Disease Cases

Sonam Raj, Rana Gopal Singh, Parimal Das


Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common, late-onset and genetically heterogenous disorder. Altered genetic background is the prime cause of ADPKD. Most of the cases showed mutations in PKD1, PKD2, GANAB and DNAJB11. Previous mutation screening studies reported that PKD1 and PKD2 are the major contributors to the disease. Among all types of DNA sequence variants, majority of the variants are protein truncating in nature. Loss of normal polycystin 1 (PC1) and polycystin 2 (PC2) proteins, encoded by PKD1 and PKD2 respectively, leads to the disease manifestation.

Methods: Three cases and 100 controls were selected for mutational screening of PKD1 and PKD2 gene using Sanger sequencing. To characterize the variants, in silico (mutation taster, Align-Grantham Variation Grantham Deviation (Align-GVGD), Polymorphism Phenotyping v2 (PolyPhen2), Protein Variation Effect Analyzer (PROVEAN), Sorting Intolerant From Tolerant (SIFT), Polycystic Kidney Disease Mutation Database (PKDB), ProtScale and protein Basic Local Alignment Search Tool (BLAST-p)) as well as in vitro (Western blot) studies were performed.

Results: We have identified a total of 14 variants (three truncating, three nonsynonymous, seven synonymous and one intronic). Three deletions (PKD1: c.445_445delC, PKD2: c.854_854delG and PKD2: c.1050_1050delC) were confirmed as rare, private and novel mutations in Indian ADPKD cases. Rest 11 variants were previously reported and likely neutral in nature. Loss of conservation of amino acid, decreased hydrophobicity and decreased coil forming ability of truncated proteins were supposed to affect the protein functions. Immunoblotting verified the expression of truncated proteins in cell.

Conclusions: We can conclude that identified deletion variants were truncating in nature and hence they were pathogenic mutations responsible for disease manifestation.

World J Nephrol Urol. 2020;9(1):15-24


ADPKD; PKD1; PKD2; Mutation; Truncated protein

Full Text: HTML PDF

Browse  Journals  


Journal of Clinical Medicine Research

Journal of Endocrinology and Metabolism

Journal of Clinical Gynecology and Obstetrics

World Journal of Oncology

Gastroenterology Research

Journal of Hematology

Journal of Medical Cases

Journal of Current Surgery

Clinical Infection and Immunity

Cardiology Research

World Journal of Nephrology and Urology

Cellular and Molecular Medicine Research

Journal of Neurology Research

International Journal of Clinical Pediatrics






World Journal of Nephrology & Urology, quarterly, ISSN 1927-1239 (print), 1927-1247 (online), published by Elmer Press Inc.                     
The content of this site is intended for health care professionals.
This is an open-access journal distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License, which permits unrestricted
non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Creative Commons Attribution license (Attribution-NonCommercial 4.0 International CC-BY-NC 4.0)

This journal follows the International Committee of Medical Journal Editors (ICMJE) recommendations for manuscripts submitted to biomedical journals,
the Committee on Publication Ethics (COPE) guidelines, and the Principles of Transparency and Best Practice in Scholarly Publishing.

website:   editorial contact:
Address: 9225 Leslie Street, Suite 201, Richmond Hill, Ontario, L4B 3H6, Canada
© Elmer Press Inc. All Rights Reserved.

Disclaimer: The views and opinions expressed in the published articles are those of the authors and do not necessarily reflect the views or opinions of the editors and Elmer Press Inc. This website is provided for medical research and informational purposes only and does not constitute any medical advice or professional services. The information provided in this journal should not be used for diagnosis and treatment, those seeking medical advice should always consult with a licensed physician.