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The utility of a genetic kidney disease clinic employing a broad range of genomic testing platforms: experience of the Irish Kidney Gene Project
BACKGROUND AND AIMS: Genetic testing presents a unique opportunity for diagnosis and management of genetic kidney diseases (GKD). Here, we describe the clinical utility and valuable impact of a specialized GKD clinic, which uses a variety of genomic sequencing strategies. METHODS: In this prospectiv...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300532/ https://www.ncbi.nlm.nih.gov/pubmed/35099770 http://dx.doi.org/10.1007/s40620-021-01236-2 |
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author | Elhassan, Elhussein A. E. Murray, Susan L. Connaughton, Dervla M. Kennedy, Claire Cormican, Sarah Cowhig, Cliona Stapleton, Caragh Little, Mark A. Kidd, Kendrah Bleyer, Anthony J. Živná, Martina Kmoch, Stanislav Fennelly, Neil K. Doyle, Brendan Dorman, Anthony Griffin, Matthew D. Casserly, Liam Harris, Peter C. Hildebrandt, Friedhelm Cavalleri, Gianpiero L. Benson, Katherine A. Conlon, Peter J. |
author_facet | Elhassan, Elhussein A. E. Murray, Susan L. Connaughton, Dervla M. Kennedy, Claire Cormican, Sarah Cowhig, Cliona Stapleton, Caragh Little, Mark A. Kidd, Kendrah Bleyer, Anthony J. Živná, Martina Kmoch, Stanislav Fennelly, Neil K. Doyle, Brendan Dorman, Anthony Griffin, Matthew D. Casserly, Liam Harris, Peter C. Hildebrandt, Friedhelm Cavalleri, Gianpiero L. Benson, Katherine A. Conlon, Peter J. |
author_sort | Elhassan, Elhussein A. E. |
collection | PubMed |
description | BACKGROUND AND AIMS: Genetic testing presents a unique opportunity for diagnosis and management of genetic kidney diseases (GKD). Here, we describe the clinical utility and valuable impact of a specialized GKD clinic, which uses a variety of genomic sequencing strategies. METHODS: In this prospective cohort study, we undertook genetic testing in adults with suspected GKD according to prespecified criteria. Over 7 years, patients were referred from tertiary centres across Ireland to an academic medical centre as part of the Irish Kidney Gene Project. RESULTS: Among 677 patients, the mean age was of 37.2 ± 13 years, and 73.9% of the patients had family history of chronic kidney disease (CKD). We achieved a molecular diagnostic rate of 50.9%. Four genes accounted for more than 70% of identified pathogenic variants: PKD1 and PKD2 (n = 186, 53.4%), MUC1 (8.9%), and COL4A5 (8.3%). In 162 patients with a genetic diagnosis, excluding PKD1/PKD2, the a priori diagnosis was confirmed in 58% and in 13% the diagnosis was reclassified. A genetic diagnosis was established in 22 (29.7%) patients with CKD of uncertain aetiology. Based on genetic testing, a diagnostic kidney biopsy was unnecessary in 13 (8%) patients. Presence of family history of CKD and the underlying a priori diagnosis were independent predictors (P < 0.001) of a positive genetic diagnosis. CONCLUSIONS: A dedicated GKD clinic is a valuable resource, and its implementation of various genomic strategies has resulted in a direct, demonstrable clinical and therapeutic benefits to affected patients. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40620-021-01236-2. |
format | Online Article Text |
id | pubmed-9300532 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-93005322022-07-22 The utility of a genetic kidney disease clinic employing a broad range of genomic testing platforms: experience of the Irish Kidney Gene Project Elhassan, Elhussein A. E. Murray, Susan L. Connaughton, Dervla M. Kennedy, Claire Cormican, Sarah Cowhig, Cliona Stapleton, Caragh Little, Mark A. Kidd, Kendrah Bleyer, Anthony J. Živná, Martina Kmoch, Stanislav Fennelly, Neil K. Doyle, Brendan Dorman, Anthony Griffin, Matthew D. Casserly, Liam Harris, Peter C. Hildebrandt, Friedhelm Cavalleri, Gianpiero L. Benson, Katherine A. Conlon, Peter J. J Nephrol original Article BACKGROUND AND AIMS: Genetic testing presents a unique opportunity for diagnosis and management of genetic kidney diseases (GKD). Here, we describe the clinical utility and valuable impact of a specialized GKD clinic, which uses a variety of genomic sequencing strategies. METHODS: In this prospective cohort study, we undertook genetic testing in adults with suspected GKD according to prespecified criteria. Over 7 years, patients were referred from tertiary centres across Ireland to an academic medical centre as part of the Irish Kidney Gene Project. RESULTS: Among 677 patients, the mean age was of 37.2 ± 13 years, and 73.9% of the patients had family history of chronic kidney disease (CKD). We achieved a molecular diagnostic rate of 50.9%. Four genes accounted for more than 70% of identified pathogenic variants: PKD1 and PKD2 (n = 186, 53.4%), MUC1 (8.9%), and COL4A5 (8.3%). In 162 patients with a genetic diagnosis, excluding PKD1/PKD2, the a priori diagnosis was confirmed in 58% and in 13% the diagnosis was reclassified. A genetic diagnosis was established in 22 (29.7%) patients with CKD of uncertain aetiology. Based on genetic testing, a diagnostic kidney biopsy was unnecessary in 13 (8%) patients. Presence of family history of CKD and the underlying a priori diagnosis were independent predictors (P < 0.001) of a positive genetic diagnosis. CONCLUSIONS: A dedicated GKD clinic is a valuable resource, and its implementation of various genomic strategies has resulted in a direct, demonstrable clinical and therapeutic benefits to affected patients. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40620-021-01236-2. Springer International Publishing 2022-01-31 2022 /pmc/articles/PMC9300532/ /pubmed/35099770 http://dx.doi.org/10.1007/s40620-021-01236-2 Text en © The Author(s) 2022 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/) . |
spellingShingle | original Article Elhassan, Elhussein A. E. Murray, Susan L. Connaughton, Dervla M. Kennedy, Claire Cormican, Sarah Cowhig, Cliona Stapleton, Caragh Little, Mark A. Kidd, Kendrah Bleyer, Anthony J. Živná, Martina Kmoch, Stanislav Fennelly, Neil K. Doyle, Brendan Dorman, Anthony Griffin, Matthew D. Casserly, Liam Harris, Peter C. Hildebrandt, Friedhelm Cavalleri, Gianpiero L. Benson, Katherine A. Conlon, Peter J. The utility of a genetic kidney disease clinic employing a broad range of genomic testing platforms: experience of the Irish Kidney Gene Project |
title | The utility of a genetic kidney disease clinic employing a broad range of genomic testing platforms: experience of the Irish Kidney Gene Project |
title_full | The utility of a genetic kidney disease clinic employing a broad range of genomic testing platforms: experience of the Irish Kidney Gene Project |
title_fullStr | The utility of a genetic kidney disease clinic employing a broad range of genomic testing platforms: experience of the Irish Kidney Gene Project |
title_full_unstemmed | The utility of a genetic kidney disease clinic employing a broad range of genomic testing platforms: experience of the Irish Kidney Gene Project |
title_short | The utility of a genetic kidney disease clinic employing a broad range of genomic testing platforms: experience of the Irish Kidney Gene Project |
title_sort | utility of a genetic kidney disease clinic employing a broad range of genomic testing platforms: experience of the irish kidney gene project |
topic | original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300532/ https://www.ncbi.nlm.nih.gov/pubmed/35099770 http://dx.doi.org/10.1007/s40620-021-01236-2 |
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