Next-Generation Sequencing-Based Genetic Diagnostic Strategies of Inherited Kidney Diseases
Background: At least 10% of adults and most of the children who receive renal replacement therapy have inherited kidney diseases. These disorders substantially decrease their life quality and have a large effect on the health-care system. Multisystem complications, with typical challenges for rare d...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Karger Publishers
2021-09-01
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| Series: | Kidney Diseases |
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| Online Access: | https://www.karger.com/Article/FullText/519095 |
| _version_ | 1818589859503144960 |
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| author | Jiahui Zhang Changming Zhang Erzhi Gao Qing Zhou |
| author_facet | Jiahui Zhang Changming Zhang Erzhi Gao Qing Zhou |
| author_sort | Jiahui Zhang |
| collection | DOAJ |
| description | Background: At least 10% of adults and most of the children who receive renal replacement therapy have inherited kidney diseases. These disorders substantially decrease their life quality and have a large effect on the health-care system. Multisystem complications, with typical challenges for rare disorders, including variable phenotypes and fragmented clinical and biological data, make genetic diagnosis of inherited kidney disorders difficult. In current clinical practice, genetic diagnosis is important for clinical management, estimating disease development, and applying personal treatment for patients. Summary: Inherited kidney diseases comprise hundreds of different disorders. Here, we have summarized various monogenic kidney disorders. These disorders are caused by mutations in genes coding for a wide range of proteins including receptors, channels/transporters, enzymes, transcription factors, and structural components that might also have a role in extrarenal organs (bone, eyes, brain, skin, ear, etc.). With the development of next-generation sequencing technologies, genetic testing and analysis become more accessible, promoting our understanding of the pathophysiologic mechanisms of inherited kidney diseases. However, challenges exist in interpreting the significance of genetic variants and translating them to guide clinical managements. Alport syndrome is chosen as an example to introduce the practical application of genetic testing and diagnosis on inherited kidney diseases, considering its clinical features, genetic backgrounds, and genetic testing for making a genetic diagnosis. Key Messages: Recent advances in genomics have highlighted the complexity of Mendelian disorders, which is due to allelic heterogeneity (distinct mutations in the same gene produce distinct phenotypes), locus heterogeneity (mutations in distinct genes result in similar phenotypes), reduced penetrance, variable expressivity, modifier genes, and/or environmental factors. Implementation of precision medicine in clinical nephrology can improve the clinical diagnostic rate and treatment efficiency of kidney diseases, which requires a good understanding of genetics for nephrologists. |
| first_indexed | 2024-12-16T09:47:21Z |
| format | Article |
| id | doaj.art-53385dec6e424745b402da911f91e372 |
| institution | Directory Open Access Journal |
| issn | 2296-9381 2296-9357 |
| language | English |
| last_indexed | 2024-12-16T09:47:21Z |
| publishDate | 2021-09-01 |
| publisher | Karger Publishers |
| record_format | Article |
| series | Kidney Diseases |
| spelling | doaj.art-53385dec6e424745b402da911f91e3722022-12-21T22:36:08ZengKarger PublishersKidney Diseases2296-93812296-93572021-09-017642543710.1159/000519095519095Next-Generation Sequencing-Based Genetic Diagnostic Strategies of Inherited Kidney DiseasesJiahui Zhang0Changming Zhang1Erzhi Gao2Qing Zhou3Life Sciences Institute, The Key Laboratory of Biosystems Homeostasis & Protection of Ministry of Education, Zhejiang University, Hangzhou, ChinaNational Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, ChinaNational Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, ChinaLife Sciences Institute, The Key Laboratory of Biosystems Homeostasis & Protection of Ministry of Education, Zhejiang University, Hangzhou, ChinaBackground: At least 10% of adults and most of the children who receive renal replacement therapy have inherited kidney diseases. These disorders substantially decrease their life quality and have a large effect on the health-care system. Multisystem complications, with typical challenges for rare disorders, including variable phenotypes and fragmented clinical and biological data, make genetic diagnosis of inherited kidney disorders difficult. In current clinical practice, genetic diagnosis is important for clinical management, estimating disease development, and applying personal treatment for patients. Summary: Inherited kidney diseases comprise hundreds of different disorders. Here, we have summarized various monogenic kidney disorders. These disorders are caused by mutations in genes coding for a wide range of proteins including receptors, channels/transporters, enzymes, transcription factors, and structural components that might also have a role in extrarenal organs (bone, eyes, brain, skin, ear, etc.). With the development of next-generation sequencing technologies, genetic testing and analysis become more accessible, promoting our understanding of the pathophysiologic mechanisms of inherited kidney diseases. However, challenges exist in interpreting the significance of genetic variants and translating them to guide clinical managements. Alport syndrome is chosen as an example to introduce the practical application of genetic testing and diagnosis on inherited kidney diseases, considering its clinical features, genetic backgrounds, and genetic testing for making a genetic diagnosis. Key Messages: Recent advances in genomics have highlighted the complexity of Mendelian disorders, which is due to allelic heterogeneity (distinct mutations in the same gene produce distinct phenotypes), locus heterogeneity (mutations in distinct genes result in similar phenotypes), reduced penetrance, variable expressivity, modifier genes, and/or environmental factors. Implementation of precision medicine in clinical nephrology can improve the clinical diagnostic rate and treatment efficiency of kidney diseases, which requires a good understanding of genetics for nephrologists.https://www.karger.com/Article/FullText/519095inherited kidney diseasesnext-generation sequencingvariants interpretationgenetic diagnosis |
| spellingShingle | Jiahui Zhang Changming Zhang Erzhi Gao Qing Zhou Next-Generation Sequencing-Based Genetic Diagnostic Strategies of Inherited Kidney Diseases Kidney Diseases inherited kidney diseases next-generation sequencing variants interpretation genetic diagnosis |
| title | Next-Generation Sequencing-Based Genetic Diagnostic Strategies of Inherited Kidney Diseases |
| title_full | Next-Generation Sequencing-Based Genetic Diagnostic Strategies of Inherited Kidney Diseases |
| title_fullStr | Next-Generation Sequencing-Based Genetic Diagnostic Strategies of Inherited Kidney Diseases |
| title_full_unstemmed | Next-Generation Sequencing-Based Genetic Diagnostic Strategies of Inherited Kidney Diseases |
| title_short | Next-Generation Sequencing-Based Genetic Diagnostic Strategies of Inherited Kidney Diseases |
| title_sort | next generation sequencing based genetic diagnostic strategies of inherited kidney diseases |
| topic | inherited kidney diseases next-generation sequencing variants interpretation genetic diagnosis |
| url | https://www.karger.com/Article/FullText/519095 |
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