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Whole exome resequencing distinguishes cystic kidney diseases from phenocopies in renal ciliopathies
Rare single-gene disorders cause chronic disease. However, half of the 6,000 recessive single gene causes of disease are still unknown. Because recessive disease genes can illuminate, at least in part, disease pathomechanism, their identification offers direct opportunities for improved clinical man...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3972265/ https://www.ncbi.nlm.nih.gov/pubmed/24257694 http://dx.doi.org/10.1038/ki.2013.450 |
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author | Gee, Heon Yung Otto, Edgar A. Hurd, Toby W. Ashraf, Shazia Chaki, Moumita Cluckey, Andrew Vega-Warner, Virginia Saisawat, Pawaree Diaz, Katrina A. Fang, Humphrey Kohl, Stefan Allen, Susan J. Airik, Rannar Zhou, Weibin Ramaswami, Gokul Janssen, Sabine Fu, Clementine Innis, Jamie L. Weber, Stefanie Vester, Udo Davis, Erica E. Katsanis, Nicholas Fathy, Hanan M. Jeck, Nikola Klaus, Gunther Nayir, Ahmet Rahim, Khawla A. Attrach, Ibrahim Al Hassoun, Ibrahim Al Ozturk, Savas Drozdz, Dorota Helmchen, Udo O’Toole, John F. Attanasio, Massimo Nürnberg, Gudrun Nürnberg, Peter Washburn, Joseph MacDonald, James James, Jeffrey W. Levy, Shawn Hildebrandt, Friedhelm |
author_facet | Gee, Heon Yung Otto, Edgar A. Hurd, Toby W. Ashraf, Shazia Chaki, Moumita Cluckey, Andrew Vega-Warner, Virginia Saisawat, Pawaree Diaz, Katrina A. Fang, Humphrey Kohl, Stefan Allen, Susan J. Airik, Rannar Zhou, Weibin Ramaswami, Gokul Janssen, Sabine Fu, Clementine Innis, Jamie L. Weber, Stefanie Vester, Udo Davis, Erica E. Katsanis, Nicholas Fathy, Hanan M. Jeck, Nikola Klaus, Gunther Nayir, Ahmet Rahim, Khawla A. Attrach, Ibrahim Al Hassoun, Ibrahim Al Ozturk, Savas Drozdz, Dorota Helmchen, Udo O’Toole, John F. Attanasio, Massimo Nürnberg, Gudrun Nürnberg, Peter Washburn, Joseph MacDonald, James James, Jeffrey W. Levy, Shawn Hildebrandt, Friedhelm |
author_sort | Gee, Heon Yung |
collection | PubMed |
description | Rare single-gene disorders cause chronic disease. However, half of the 6,000 recessive single gene causes of disease are still unknown. Because recessive disease genes can illuminate, at least in part, disease pathomechanism, their identification offers direct opportunities for improved clinical management and potentially treatment. Rare diseases comprise the majority of chronic kidney disease (CKD) in children but are notoriously difficult to diagnose. Whole exome resequencing facilitates identification of recessive disease genes. However, its utility is impeded by the large number of genetic variants detected. We here overcome this limitation by combining homozygosity mapping with whole exome resequencing in 10 sib pairs with a nephronophthisis-related ciliopathy, which represents the most frequent genetic cause of CKD in the first three decades of life. In 7 of 10 sib-ships with a histologic or ultrasonographic diagnosis of nephronophthisis-related ciliopathy we detect the causative gene. In six sib-ships we identify mutations of known nephronophthisis-related ciliopathy genes, while in two additional sib-ships we found mutations in the known CKD-causing genes SLC4A1 and AGXT as phenocopies of nephronophthisis-related ciliopathy. Thus whole exome resequencing establishes an efficient, non-invasive approach towards early detection and causation-based diagnosis of rare kidney diseases. This approach can be extended to other rare recessive disorders, thereby providing accurate diagnosis and facilitating the study of disease mechanisms. |
format | Online Article Text |
id | pubmed-3972265 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
record_format | MEDLINE/PubMed |
spelling | pubmed-39722652014-10-01 Whole exome resequencing distinguishes cystic kidney diseases from phenocopies in renal ciliopathies Gee, Heon Yung Otto, Edgar A. Hurd, Toby W. Ashraf, Shazia Chaki, Moumita Cluckey, Andrew Vega-Warner, Virginia Saisawat, Pawaree Diaz, Katrina A. Fang, Humphrey Kohl, Stefan Allen, Susan J. Airik, Rannar Zhou, Weibin Ramaswami, Gokul Janssen, Sabine Fu, Clementine Innis, Jamie L. Weber, Stefanie Vester, Udo Davis, Erica E. Katsanis, Nicholas Fathy, Hanan M. Jeck, Nikola Klaus, Gunther Nayir, Ahmet Rahim, Khawla A. Attrach, Ibrahim Al Hassoun, Ibrahim Al Ozturk, Savas Drozdz, Dorota Helmchen, Udo O’Toole, John F. Attanasio, Massimo Nürnberg, Gudrun Nürnberg, Peter Washburn, Joseph MacDonald, James James, Jeffrey W. Levy, Shawn Hildebrandt, Friedhelm Kidney Int Article Rare single-gene disorders cause chronic disease. However, half of the 6,000 recessive single gene causes of disease are still unknown. Because recessive disease genes can illuminate, at least in part, disease pathomechanism, their identification offers direct opportunities for improved clinical management and potentially treatment. Rare diseases comprise the majority of chronic kidney disease (CKD) in children but are notoriously difficult to diagnose. Whole exome resequencing facilitates identification of recessive disease genes. However, its utility is impeded by the large number of genetic variants detected. We here overcome this limitation by combining homozygosity mapping with whole exome resequencing in 10 sib pairs with a nephronophthisis-related ciliopathy, which represents the most frequent genetic cause of CKD in the first three decades of life. In 7 of 10 sib-ships with a histologic or ultrasonographic diagnosis of nephronophthisis-related ciliopathy we detect the causative gene. In six sib-ships we identify mutations of known nephronophthisis-related ciliopathy genes, while in two additional sib-ships we found mutations in the known CKD-causing genes SLC4A1 and AGXT as phenocopies of nephronophthisis-related ciliopathy. Thus whole exome resequencing establishes an efficient, non-invasive approach towards early detection and causation-based diagnosis of rare kidney diseases. This approach can be extended to other rare recessive disorders, thereby providing accurate diagnosis and facilitating the study of disease mechanisms. 2013-11-20 2014-04 /pmc/articles/PMC3972265/ /pubmed/24257694 http://dx.doi.org/10.1038/ki.2013.450 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Gee, Heon Yung Otto, Edgar A. Hurd, Toby W. Ashraf, Shazia Chaki, Moumita Cluckey, Andrew Vega-Warner, Virginia Saisawat, Pawaree Diaz, Katrina A. Fang, Humphrey Kohl, Stefan Allen, Susan J. Airik, Rannar Zhou, Weibin Ramaswami, Gokul Janssen, Sabine Fu, Clementine Innis, Jamie L. Weber, Stefanie Vester, Udo Davis, Erica E. Katsanis, Nicholas Fathy, Hanan M. Jeck, Nikola Klaus, Gunther Nayir, Ahmet Rahim, Khawla A. Attrach, Ibrahim Al Hassoun, Ibrahim Al Ozturk, Savas Drozdz, Dorota Helmchen, Udo O’Toole, John F. Attanasio, Massimo Nürnberg, Gudrun Nürnberg, Peter Washburn, Joseph MacDonald, James James, Jeffrey W. Levy, Shawn Hildebrandt, Friedhelm Whole exome resequencing distinguishes cystic kidney diseases from phenocopies in renal ciliopathies |
title | Whole exome resequencing distinguishes cystic kidney diseases from
phenocopies in renal ciliopathies |
title_full | Whole exome resequencing distinguishes cystic kidney diseases from
phenocopies in renal ciliopathies |
title_fullStr | Whole exome resequencing distinguishes cystic kidney diseases from
phenocopies in renal ciliopathies |
title_full_unstemmed | Whole exome resequencing distinguishes cystic kidney diseases from
phenocopies in renal ciliopathies |
title_short | Whole exome resequencing distinguishes cystic kidney diseases from
phenocopies in renal ciliopathies |
title_sort | whole exome resequencing distinguishes cystic kidney diseases from
phenocopies in renal ciliopathies |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3972265/ https://www.ncbi.nlm.nih.gov/pubmed/24257694 http://dx.doi.org/10.1038/ki.2013.450 |
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