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Case Report: A Novel In-Frame Deletion of GLIS2 Leading to Nephronophthisis and Early Onset Kidney Failure

Variants in the GLIS family zinc finger protein 2 (GLIS2) are a rare cause of nephronophthisis-related ciliopathies (NPHP-RC). A reduction in urinary concentration and a progressive chronic tubulointerstitial nephropathy with corticomedullary cysts are the major characteristic features of NPHP. NPHP...

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Autores principales: Al Alawi, Intisar, Powell, Laura, Rice, Sarah J., Al Riyami, Mohammed S., Al-Riyami, Marwa, Al Salmi, Issa, Sayer, John A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8669607/
https://www.ncbi.nlm.nih.gov/pubmed/34917135
http://dx.doi.org/10.3389/fgene.2021.791495
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author Al Alawi, Intisar
Powell, Laura
Rice, Sarah J.
Al Riyami, Mohammed S.
Al-Riyami, Marwa
Al Salmi, Issa
Sayer, John A.
author_facet Al Alawi, Intisar
Powell, Laura
Rice, Sarah J.
Al Riyami, Mohammed S.
Al-Riyami, Marwa
Al Salmi, Issa
Sayer, John A.
author_sort Al Alawi, Intisar
collection PubMed
description Variants in the GLIS family zinc finger protein 2 (GLIS2) are a rare cause of nephronophthisis-related ciliopathies (NPHP-RC). A reduction in urinary concentration and a progressive chronic tubulointerstitial nephropathy with corticomedullary cysts are the major characteristic features of NPHP. NPHP demonstrates phenotypic and genetic heterogeneity with at least 25 different recessive genes associated with the disease. We report a female, from a consanguineous family, who presented age 9 years with echogenic kidneys with loss of cortico-medullary differentiation and progressive chronic kidney disease reaching kidney failure by 10 years of age. A novel homozygous in-frame deletion (NM_032,575.3: c.560_574delACCATGTCAACGATT, p.H188_Y192del) in GLIS2 was identified using whole exome sequencing (WES) that segregated from each parent. The five amino acid deletion disrupts the alpha-helix of GLIS2 zinc-finger motif with predicted misfolding of the protein leading to its predicted pathogenicity. This study broadens the variant spectrum of GLIS2 variants leading to NPHP-RC. WES is a suitable molecular tool for children with kidney failure suggestive of NPHP-RC and should be part of routine diagnostics in kidney failure of unknown cause, especially in consanguineous families.
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spelling pubmed-86696072021-12-15 Case Report: A Novel In-Frame Deletion of GLIS2 Leading to Nephronophthisis and Early Onset Kidney Failure Al Alawi, Intisar Powell, Laura Rice, Sarah J. Al Riyami, Mohammed S. Al-Riyami, Marwa Al Salmi, Issa Sayer, John A. Front Genet Genetics Variants in the GLIS family zinc finger protein 2 (GLIS2) are a rare cause of nephronophthisis-related ciliopathies (NPHP-RC). A reduction in urinary concentration and a progressive chronic tubulointerstitial nephropathy with corticomedullary cysts are the major characteristic features of NPHP. NPHP demonstrates phenotypic and genetic heterogeneity with at least 25 different recessive genes associated with the disease. We report a female, from a consanguineous family, who presented age 9 years with echogenic kidneys with loss of cortico-medullary differentiation and progressive chronic kidney disease reaching kidney failure by 10 years of age. A novel homozygous in-frame deletion (NM_032,575.3: c.560_574delACCATGTCAACGATT, p.H188_Y192del) in GLIS2 was identified using whole exome sequencing (WES) that segregated from each parent. The five amino acid deletion disrupts the alpha-helix of GLIS2 zinc-finger motif with predicted misfolding of the protein leading to its predicted pathogenicity. This study broadens the variant spectrum of GLIS2 variants leading to NPHP-RC. WES is a suitable molecular tool for children with kidney failure suggestive of NPHP-RC and should be part of routine diagnostics in kidney failure of unknown cause, especially in consanguineous families. Frontiers Media S.A. 2021-11-30 /pmc/articles/PMC8669607/ /pubmed/34917135 http://dx.doi.org/10.3389/fgene.2021.791495 Text en Copyright © 2021 Al Alawi, Powell, Rice, Al Riyami, Al-Riyami, Al Salmi and Sayer. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Al Alawi, Intisar
Powell, Laura
Rice, Sarah J.
Al Riyami, Mohammed S.
Al-Riyami, Marwa
Al Salmi, Issa
Sayer, John A.
Case Report: A Novel In-Frame Deletion of GLIS2 Leading to Nephronophthisis and Early Onset Kidney Failure
title Case Report: A Novel In-Frame Deletion of GLIS2 Leading to Nephronophthisis and Early Onset Kidney Failure
title_full Case Report: A Novel In-Frame Deletion of GLIS2 Leading to Nephronophthisis and Early Onset Kidney Failure
title_fullStr Case Report: A Novel In-Frame Deletion of GLIS2 Leading to Nephronophthisis and Early Onset Kidney Failure
title_full_unstemmed Case Report: A Novel In-Frame Deletion of GLIS2 Leading to Nephronophthisis and Early Onset Kidney Failure
title_short Case Report: A Novel In-Frame Deletion of GLIS2 Leading to Nephronophthisis and Early Onset Kidney Failure
title_sort case report: a novel in-frame deletion of glis2 leading to nephronophthisis and early onset kidney failure
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8669607/
https://www.ncbi.nlm.nih.gov/pubmed/34917135
http://dx.doi.org/10.3389/fgene.2021.791495
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