ESPN 53rd Annual Meeting

ESPN 2021

Next Generation Sequencing (NGS) data among children from eastern India with suspected inherited tubular disorder: East Zone Tubulopathy Genetic Study
RAJIV SINHA 1 Kausik Mandal 2 Subal Pradhan 3 Sushmita Banerjee 4 Afsana Jahan 6 Ramprasad V 7 Amitava Pahari 5

3- SVPPGI, Cuttack
4- CMRI, KOlkata
5- Apollo Hospital, Kolkata
6- Pratiksha Hospital, Gauhati
7- Medgenome


Currently data are scarce on tubulopathy genotype among Indian population. We hereby present Next Generation Sequencing (NGS) generated phenotype-genotype data among children with suspected tubular disorder from Eastern India.

Material and methods:

A prospective observational multi-centric study was conducted across 5 paediatric nephrology centres. After formal counselling and consent children (<18 years) with clinically suspected tubular disorders underwent NGS. Variants were classified as per American College of Medical Genetics (2015) guidelines and pathogenic / likely pathogenic variants were considered significant.


77 index cases (median age 46, IQR 18 to 10 months; male 74% n=57) underwent NGS.  Phenotypic classifications were as follows: Distal Renal Tubular Acidosis i.e. RTA (n=24), Bartter (n=19), Isolated hypophosphatemic rickets with phosphaturia (n=6), Proximal RTA (n=12), Nephrogenic Diabetes Insipidus (n=7), Kidney stone / Nephrocalcinosis (n=5) and Miscellaneous (n=4). Among them 58 children (75%) had 53 pathogenic or likely pathogenic variants (33 novel) detected. Percentage NGS yield was noted to be in 80’s for most of the phenotypes except distal RTA (71%) and stone /nephrocalcinosis (20%). NGS resulted in a new diagnosis in 9 children including non-tubulopathy disorder mimicking as tubulopathy in 7 children (Cystic fibrosis presenting with Bartter phenotype; n=4 and one each of Cong chloride diarrhea with Bartter phenotype, Nephronopthisis with Nephrogenic Diabetes Insipidus phenotype  and Hypo-parathyroidism, sensori-neural deafness and renal dysplasia phenotype mimicking miscellaneous tubulopathy). Additional change of diagnosis happened in two children (Bartter phenotype to Gitelman syndrome and Nephrogenic Diabetes Insipidus phenotype to distal RTA).


In our cohort of suspected tubulopathy from Eastern India NGS had a yield of 75%, identified a large number of novel variants and resulted in 12 % (n=9) new diagnosis. Our finding underscores the clinical utility of NGS for suspected tubulopathy and also highlights the unique mutation spectrum in Indian population and need for larger Indian studies.