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Case Report: Unusual Aggregation of Different Glomerulopathies in a Family Resolved by Genetic Testing and Reverse Phenotyping

Glomerular diseases (GDs) are a major cause of chronic kidney disease in children. The conventional approach to diagnosis of GDs includes clinical evaluation and, in most cases, kidney biopsy to make a definitive diagnosis. However, in many cases, clinical presentations of different GDs can overlap,...

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Autores principales: Kumar, Reeti, Keskinyan, Vahakn, Stangl, Megan Chryst, Lane, Brandon M., Buckley, Anne F., Barisoni, Laura, Howell, David N., Gbadegesin, Rasheed A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8918647/
https://www.ncbi.nlm.nih.gov/pubmed/35295700
http://dx.doi.org/10.3389/fped.2022.826330
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author Kumar, Reeti
Keskinyan, Vahakn
Stangl, Megan Chryst
Lane, Brandon M.
Buckley, Anne F.
Barisoni, Laura
Howell, David N.
Gbadegesin, Rasheed A.
author_facet Kumar, Reeti
Keskinyan, Vahakn
Stangl, Megan Chryst
Lane, Brandon M.
Buckley, Anne F.
Barisoni, Laura
Howell, David N.
Gbadegesin, Rasheed A.
author_sort Kumar, Reeti
collection PubMed
description Glomerular diseases (GDs) are a major cause of chronic kidney disease in children. The conventional approach to diagnosis of GDs includes clinical evaluation and, in most cases, kidney biopsy to make a definitive diagnosis. However, in many cases, clinical presentations of different GDs can overlap, leading to uncertainty in diagnosis and management even after renal biopsy. In this report, we identify a family with clinical diagnoses of postinfectious glomerulonephritis and IgA nephropathy in a parent and two children. Renal biopsies were initially inconclusive; however, genetic testing showed that the two individuals diagnosed at different points with IgA nephropathy carried novel segregating pathogenic variants in COL4A5 gene. We were only able to make the final diagnoses in each of the family members after genetic testing and reverse phenotyping. This case highlights the utility of genetic testing and reverse phenotyping in resolving clinical diagnosis in families with unusual constellations of different glomerulopathies. We propose that clustering of different glomerular disease phenotypes in a family should be an indication for genetic testing followed by reverse phenotyping.
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spelling pubmed-89186472022-03-15 Case Report: Unusual Aggregation of Different Glomerulopathies in a Family Resolved by Genetic Testing and Reverse Phenotyping Kumar, Reeti Keskinyan, Vahakn Stangl, Megan Chryst Lane, Brandon M. Buckley, Anne F. Barisoni, Laura Howell, David N. Gbadegesin, Rasheed A. Front Pediatr Pediatrics Glomerular diseases (GDs) are a major cause of chronic kidney disease in children. The conventional approach to diagnosis of GDs includes clinical evaluation and, in most cases, kidney biopsy to make a definitive diagnosis. However, in many cases, clinical presentations of different GDs can overlap, leading to uncertainty in diagnosis and management even after renal biopsy. In this report, we identify a family with clinical diagnoses of postinfectious glomerulonephritis and IgA nephropathy in a parent and two children. Renal biopsies were initially inconclusive; however, genetic testing showed that the two individuals diagnosed at different points with IgA nephropathy carried novel segregating pathogenic variants in COL4A5 gene. We were only able to make the final diagnoses in each of the family members after genetic testing and reverse phenotyping. This case highlights the utility of genetic testing and reverse phenotyping in resolving clinical diagnosis in families with unusual constellations of different glomerulopathies. We propose that clustering of different glomerular disease phenotypes in a family should be an indication for genetic testing followed by reverse phenotyping. Frontiers Media S.A. 2022-02-28 /pmc/articles/PMC8918647/ /pubmed/35295700 http://dx.doi.org/10.3389/fped.2022.826330 Text en Copyright © 2022 Kumar, Keskinyan, Stangl, Lane, Buckley, Barisoni, Howell and Gbadegesin. 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 Pediatrics
Kumar, Reeti
Keskinyan, Vahakn
Stangl, Megan Chryst
Lane, Brandon M.
Buckley, Anne F.
Barisoni, Laura
Howell, David N.
Gbadegesin, Rasheed A.
Case Report: Unusual Aggregation of Different Glomerulopathies in a Family Resolved by Genetic Testing and Reverse Phenotyping
title Case Report: Unusual Aggregation of Different Glomerulopathies in a Family Resolved by Genetic Testing and Reverse Phenotyping
title_full Case Report: Unusual Aggregation of Different Glomerulopathies in a Family Resolved by Genetic Testing and Reverse Phenotyping
title_fullStr Case Report: Unusual Aggregation of Different Glomerulopathies in a Family Resolved by Genetic Testing and Reverse Phenotyping
title_full_unstemmed Case Report: Unusual Aggregation of Different Glomerulopathies in a Family Resolved by Genetic Testing and Reverse Phenotyping
title_short Case Report: Unusual Aggregation of Different Glomerulopathies in a Family Resolved by Genetic Testing and Reverse Phenotyping
title_sort case report: unusual aggregation of different glomerulopathies in a family resolved by genetic testing and reverse phenotyping
topic Pediatrics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8918647/
https://www.ncbi.nlm.nih.gov/pubmed/35295700
http://dx.doi.org/10.3389/fped.2022.826330
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