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Deciphering the mutation spectrum in south Indian children with congenital anomalies of the kidney and urinary tract

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) cover a spectrum of structural malformations that result from aberrant morphogenesis of kidney and urinary tract. It is the most prevalent cause of kidney failure in children. Hence, it is important from a clinical perspective...

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Autores principales: Narikot, Ambili, Pardeshi, Varsha Chhotusing, Shubha, A. M., Iyengar, Arpana, Vasudevan, Anil
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8722277/
https://www.ncbi.nlm.nih.gov/pubmed/34979951
http://dx.doi.org/10.1186/s12882-021-02628-z
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author Narikot, Ambili
Pardeshi, Varsha Chhotusing
Shubha, A. M.
Iyengar, Arpana
Vasudevan, Anil
author_facet Narikot, Ambili
Pardeshi, Varsha Chhotusing
Shubha, A. M.
Iyengar, Arpana
Vasudevan, Anil
author_sort Narikot, Ambili
collection PubMed
description BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) cover a spectrum of structural malformations that result from aberrant morphogenesis of kidney and urinary tract. It is the most prevalent cause of kidney failure in children. Hence, it is important from a clinical perspective to unravel the molecular etiology of kidney and urinary tract malformations. Causal variants in genes that direct various stages of development of kidney and urinary tract in fetal life have been identified in 5–20% of CAKUT patients from Western countries. Recent advances in next generation sequencing technology and decreasing cost offer the opportunity to characterize the genetic profile of CAKUT in Indian population and facilitate integration of genetic diagnostics in care of children with CAKUT. METHODS: Customized targeted panel sequencing was performed to identify pathogenic variants in 31 genes known to cause human CAKUT in 69 south Indian children with CAKUT. The NGS data was filtered using standardized pipeline and the variants were classified using ACMG criteria. Genotype and phenotype correlations were performed. RESULTS: The cohort consisted of children mostly with posterior urethral valve (PUV) (39.1%), vesico-ureteric reflux (VUR) (33.3%) and multi-cystic dysplastic kidney (MCDK) (7.2%). No pathogenic or likely pathogenic variants were identified in the study. Most of our variants (n = 39, 60%) were variants of unknown significance with 25.6% (10/39) of them were identified as potentially damaging but were novel variants. CONCLUSIONS: The present study did not identify any disease-causing monogenic variants in the cohort. The absence of genetic cause may be due to limitations of panel-based testing and also due to higher proportion of children with abnormalities in lower urinary tract than hypodysplasia of kidneys. Clinical, larger targeted panel or whole exome sequencing may be a better method to characterize the genetic profile of Indians patients with CAKUT. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12882-021-02628-z.
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spelling pubmed-87222772022-01-06 Deciphering the mutation spectrum in south Indian children with congenital anomalies of the kidney and urinary tract Narikot, Ambili Pardeshi, Varsha Chhotusing Shubha, A. M. Iyengar, Arpana Vasudevan, Anil BMC Nephrol Research BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) cover a spectrum of structural malformations that result from aberrant morphogenesis of kidney and urinary tract. It is the most prevalent cause of kidney failure in children. Hence, it is important from a clinical perspective to unravel the molecular etiology of kidney and urinary tract malformations. Causal variants in genes that direct various stages of development of kidney and urinary tract in fetal life have been identified in 5–20% of CAKUT patients from Western countries. Recent advances in next generation sequencing technology and decreasing cost offer the opportunity to characterize the genetic profile of CAKUT in Indian population and facilitate integration of genetic diagnostics in care of children with CAKUT. METHODS: Customized targeted panel sequencing was performed to identify pathogenic variants in 31 genes known to cause human CAKUT in 69 south Indian children with CAKUT. The NGS data was filtered using standardized pipeline and the variants were classified using ACMG criteria. Genotype and phenotype correlations were performed. RESULTS: The cohort consisted of children mostly with posterior urethral valve (PUV) (39.1%), vesico-ureteric reflux (VUR) (33.3%) and multi-cystic dysplastic kidney (MCDK) (7.2%). No pathogenic or likely pathogenic variants were identified in the study. Most of our variants (n = 39, 60%) were variants of unknown significance with 25.6% (10/39) of them were identified as potentially damaging but were novel variants. CONCLUSIONS: The present study did not identify any disease-causing monogenic variants in the cohort. The absence of genetic cause may be due to limitations of panel-based testing and also due to higher proportion of children with abnormalities in lower urinary tract than hypodysplasia of kidneys. Clinical, larger targeted panel or whole exome sequencing may be a better method to characterize the genetic profile of Indians patients with CAKUT. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12882-021-02628-z. BioMed Central 2022-01-03 /pmc/articles/PMC8722277/ /pubmed/34979951 http://dx.doi.org/10.1186/s12882-021-02628-z Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Narikot, Ambili
Pardeshi, Varsha Chhotusing
Shubha, A. M.
Iyengar, Arpana
Vasudevan, Anil
Deciphering the mutation spectrum in south Indian children with congenital anomalies of the kidney and urinary tract
title Deciphering the mutation spectrum in south Indian children with congenital anomalies of the kidney and urinary tract
title_full Deciphering the mutation spectrum in south Indian children with congenital anomalies of the kidney and urinary tract
title_fullStr Deciphering the mutation spectrum in south Indian children with congenital anomalies of the kidney and urinary tract
title_full_unstemmed Deciphering the mutation spectrum in south Indian children with congenital anomalies of the kidney and urinary tract
title_short Deciphering the mutation spectrum in south Indian children with congenital anomalies of the kidney and urinary tract
title_sort deciphering the mutation spectrum in south indian children with congenital anomalies of the kidney and urinary tract
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8722277/
https://www.ncbi.nlm.nih.gov/pubmed/34979951
http://dx.doi.org/10.1186/s12882-021-02628-z
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