Eintrag weiter verarbeiten
Targeted Exome Sequencing Identifies PBX1 as Involved in Monogenic Congenital Anomalies of the Kidney and Urinary Tract
Gespeichert in:
| Zeitschriftentitel: | Journal of the American Society of Nephrology |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , , , , , , , , , , , , , , |
| In: | Journal of the American Society of Nephrology, 28, 2017, 10, S. 2901-2914 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Ovid Technologies (Wolters Kluwer Health)
|
| Schlagwörter: |
| author_facet |
Heidet, Laurence Morinière, Vincent Henry, Charline De Tomasi, Lara Reilly, Madeline Louise Humbert, Camille Alibeu, Olivier Fourrage, Cécile Bole-Feysot, Christine Nitschké, Patrick Tores, Frédéric Bras, Marc Jeanpierre, Marc Pietrement, Christine Gaillard, Dominique Gonzales, Marie Novo, Robert Schaefer, Elise Roume, Joëlle Martinovic, Jelena Malan, Valérie Salomon, Rémi Saunier, Sophie Antignac, Corinne Jeanpierre, Cécile Heidet, Laurence Morinière, Vincent Henry, Charline De Tomasi, Lara Reilly, Madeline Louise Humbert, Camille Alibeu, Olivier Fourrage, Cécile Bole-Feysot, Christine Nitschké, Patrick Tores, Frédéric Bras, Marc Jeanpierre, Marc Pietrement, Christine Gaillard, Dominique Gonzales, Marie Novo, Robert Schaefer, Elise Roume, Joëlle Martinovic, Jelena Malan, Valérie Salomon, Rémi Saunier, Sophie Antignac, Corinne Jeanpierre, Cécile |
|---|---|
| author |
Heidet, Laurence Morinière, Vincent Henry, Charline De Tomasi, Lara Reilly, Madeline Louise Humbert, Camille Alibeu, Olivier Fourrage, Cécile Bole-Feysot, Christine Nitschké, Patrick Tores, Frédéric Bras, Marc Jeanpierre, Marc Pietrement, Christine Gaillard, Dominique Gonzales, Marie Novo, Robert Schaefer, Elise Roume, Joëlle Martinovic, Jelena Malan, Valérie Salomon, Rémi Saunier, Sophie Antignac, Corinne Jeanpierre, Cécile |
| spellingShingle |
Heidet, Laurence Morinière, Vincent Henry, Charline De Tomasi, Lara Reilly, Madeline Louise Humbert, Camille Alibeu, Olivier Fourrage, Cécile Bole-Feysot, Christine Nitschké, Patrick Tores, Frédéric Bras, Marc Jeanpierre, Marc Pietrement, Christine Gaillard, Dominique Gonzales, Marie Novo, Robert Schaefer, Elise Roume, Joëlle Martinovic, Jelena Malan, Valérie Salomon, Rémi Saunier, Sophie Antignac, Corinne Jeanpierre, Cécile Journal of the American Society of Nephrology Targeted Exome Sequencing Identifies PBX1 as Involved in Monogenic Congenital Anomalies of the Kidney and Urinary Tract Nephrology General Medicine |
| author_sort |
heidet, laurence |
| spelling |
Heidet, Laurence Morinière, Vincent Henry, Charline De Tomasi, Lara Reilly, Madeline Louise Humbert, Camille Alibeu, Olivier Fourrage, Cécile Bole-Feysot, Christine Nitschké, Patrick Tores, Frédéric Bras, Marc Jeanpierre, Marc Pietrement, Christine Gaillard, Dominique Gonzales, Marie Novo, Robert Schaefer, Elise Roume, Joëlle Martinovic, Jelena Malan, Valérie Salomon, Rémi Saunier, Sophie Antignac, Corinne Jeanpierre, Cécile 1046-6673 1533-3450 Ovid Technologies (Wolters Kluwer Health) Nephrology General Medicine http://dx.doi.org/10.1681/asn.2017010043 <jats:p>Congenital anomalies of the kidney and urinary tract (CAKUT) occur in three to six of 1000 live births, represent about 20% of the prenatally detected anomalies, and constitute the main cause of CKD in children. These disorders are phenotypically and genetically heterogeneous. Monogenic causes of CAKUT in humans and mice have been identified. However, despite high-throughput sequencing studies, the cause of the disease remains unknown in most patients, and several studies support more complex inheritance and the role of environmental factors and/or epigenetics in the pathophysiology of CAKUT. Here, we report the targeted exome sequencing of 330 genes, including genes known to be involved in CAKUT and candidate genes, in a cohort of 204 unrelated patients with CAKUT; 45% of the patients were severe fetal cases. We identified pathogenic mutations in 36 of 204 (17.6%) patients. These mutations included five <jats:italic toggle="yes">de novo</jats:italic> heterozygous loss of function mutations/deletions in the PBX homeobox 1 gene (<jats:italic toggle="yes">PBX1</jats:italic>), a gene known to have a crucial role in kidney development. In contrast, the frequency of <jats:italic toggle="yes">SOX17</jats:italic> and <jats:italic toggle="yes">DSTYK</jats:italic> variants recently reported as pathogenic in CAKUT did not indicate causality. These findings suggest that <jats:italic toggle="yes">PBX1</jats:italic> is involved in monogenic CAKUT in humans and call into question the role of some gene variants recently reported as pathogenic in CAKUT. Targeted exome sequencing also proved to be an efficient and cost-effective strategy to identify pathogenic mutations and deletions in known CAKUT genes.</jats:p> Targeted Exome Sequencing Identifies PBX1 as Involved in Monogenic Congenital Anomalies of the Kidney and Urinary Tract Journal of the American Society of Nephrology |
| doi_str_mv |
10.1681/asn.2017010043 |
| facet_avail |
Online Free |
| finc_class_facet |
Medizin |
| format |
ElectronicArticle |
| fullrecord |
blob:ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTY4MS9hc24uMjAxNzAxMDA0Mw |
| id |
ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTY4MS9hc24uMjAxNzAxMDA0Mw |
| institution |
DE-105 DE-14 DE-Ch1 DE-L229 DE-D275 DE-Bn3 DE-Brt1 DE-Zwi2 DE-D161 DE-Gla1 DE-Zi4 DE-15 DE-Pl11 DE-Rs1 |
| imprint |
Ovid Technologies (Wolters Kluwer Health), 2017 |
| imprint_str_mv |
Ovid Technologies (Wolters Kluwer Health), 2017 |
| issn |
1046-6673 1533-3450 |
| issn_str_mv |
1046-6673 1533-3450 |
| language |
English |
| mega_collection |
Ovid Technologies (Wolters Kluwer Health) (CrossRef) |
| match_str |
heidet2017targetedexomesequencingidentifiespbx1asinvolvedinmonogeniccongenitalanomaliesofthekidneyandurinarytract |
| publishDateSort |
2017 |
| publisher |
Ovid Technologies (Wolters Kluwer Health) |
| recordtype |
ai |
| record_format |
ai |
| series |
Journal of the American Society of Nephrology |
| source_id |
49 |
| title |
Targeted Exome Sequencing Identifies PBX1 as Involved in Monogenic Congenital Anomalies of the Kidney and Urinary Tract |
| title_unstemmed |
Targeted Exome Sequencing Identifies PBX1 as Involved in Monogenic Congenital Anomalies of the Kidney and Urinary Tract |
| title_full |
Targeted Exome Sequencing Identifies PBX1 as Involved in Monogenic Congenital Anomalies of the Kidney and Urinary Tract |
| title_fullStr |
Targeted Exome Sequencing Identifies PBX1 as Involved in Monogenic Congenital Anomalies of the Kidney and Urinary Tract |
| title_full_unstemmed |
Targeted Exome Sequencing Identifies PBX1 as Involved in Monogenic Congenital Anomalies of the Kidney and Urinary Tract |
| title_short |
Targeted Exome Sequencing Identifies PBX1 as Involved in Monogenic Congenital Anomalies of the Kidney and Urinary Tract |
| title_sort |
targeted exome sequencing identifies pbx1 as involved in monogenic congenital anomalies of the kidney and urinary tract |
| topic |
Nephrology General Medicine |
| url |
http://dx.doi.org/10.1681/asn.2017010043 |
| publishDate |
2017 |
| physical |
2901-2914 |
| description |
<jats:p>Congenital anomalies of the kidney and urinary tract (CAKUT) occur in three to six of 1000 live births, represent about 20% of the prenatally detected anomalies, and constitute the main cause of CKD in children. These disorders are phenotypically and genetically heterogeneous. Monogenic causes of CAKUT in humans and mice have been identified. However, despite high-throughput sequencing studies, the cause of the disease remains unknown in most patients, and several studies support more complex inheritance and the role of environmental factors and/or epigenetics in the pathophysiology of CAKUT. Here, we report the targeted exome sequencing of 330 genes, including genes known to be involved in CAKUT and candidate genes, in a cohort of 204 unrelated patients with CAKUT; 45% of the patients were severe fetal cases. We identified pathogenic mutations in 36 of 204 (17.6%) patients. These mutations included five <jats:italic toggle="yes">de novo</jats:italic> heterozygous loss of function mutations/deletions in the PBX homeobox 1 gene (<jats:italic toggle="yes">PBX1</jats:italic>), a gene known to have a crucial role in kidney development. In contrast, the frequency of <jats:italic toggle="yes">SOX17</jats:italic> and <jats:italic toggle="yes">DSTYK</jats:italic> variants recently reported as pathogenic in CAKUT did not indicate causality. These findings suggest that <jats:italic toggle="yes">PBX1</jats:italic> is involved in monogenic CAKUT in humans and call into question the role of some gene variants recently reported as pathogenic in CAKUT. Targeted exome sequencing also proved to be an efficient and cost-effective strategy to identify pathogenic mutations and deletions in known CAKUT genes.</jats:p> |
| container_issue |
10 |
| container_start_page |
2901 |
| container_title |
Journal of the American Society of Nephrology |
| container_volume |
28 |
| format_de105 |
Article, E-Article |
| format_de14 |
Article, E-Article |
| format_de15 |
Article, E-Article |
| format_de520 |
Article, E-Article |
| format_de540 |
Article, E-Article |
| format_dech1 |
Article, E-Article |
| format_ded117 |
Article, E-Article |
| format_degla1 |
E-Article |
| format_del152 |
Buch |
| format_del189 |
Article, E-Article |
| format_dezi4 |
Article |
| format_dezwi2 |
Article, E-Article |
| format_finc |
Article, E-Article |
| format_nrw |
Article, E-Article |
| _version_ |
1792341140183187464 |
| geogr_code |
not assigned |
| last_indexed |
2024-03-01T16:15:11.424Z |
| geogr_code_person |
not assigned |
| openURL |
url_ver=Z39.88-2004&ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fvufind.svn.sourceforge.net%3Agenerator&rft.title=Targeted+Exome+Sequencing+Identifies+PBX1+as+Involved+in+Monogenic+Congenital+Anomalies+of+the+Kidney+and+Urinary+Tract&rft.date=2017-10-01&genre=article&issn=1533-3450&volume=28&issue=10&spage=2901&epage=2914&pages=2901-2914&jtitle=Journal+of+the+American+Society+of+Nephrology&atitle=Targeted+Exome+Sequencing+Identifies+PBX1+as+Involved+in+Monogenic+Congenital+Anomalies+of+the+Kidney+and+Urinary+Tract&aulast=Jeanpierre&aufirst=C%C3%A9cile&rft_id=info%3Adoi%2F10.1681%2Fasn.2017010043&rft.language%5B0%5D=eng |
| SOLR | |
| _version_ | 1792341140183187464 |
| author | Heidet, Laurence, Morinière, Vincent, Henry, Charline, De Tomasi, Lara, Reilly, Madeline Louise, Humbert, Camille, Alibeu, Olivier, Fourrage, Cécile, Bole-Feysot, Christine, Nitschké, Patrick, Tores, Frédéric, Bras, Marc, Jeanpierre, Marc, Pietrement, Christine, Gaillard, Dominique, Gonzales, Marie, Novo, Robert, Schaefer, Elise, Roume, Joëlle, Martinovic, Jelena, Malan, Valérie, Salomon, Rémi, Saunier, Sophie, Antignac, Corinne, Jeanpierre, Cécile |
| author_facet | Heidet, Laurence, Morinière, Vincent, Henry, Charline, De Tomasi, Lara, Reilly, Madeline Louise, Humbert, Camille, Alibeu, Olivier, Fourrage, Cécile, Bole-Feysot, Christine, Nitschké, Patrick, Tores, Frédéric, Bras, Marc, Jeanpierre, Marc, Pietrement, Christine, Gaillard, Dominique, Gonzales, Marie, Novo, Robert, Schaefer, Elise, Roume, Joëlle, Martinovic, Jelena, Malan, Valérie, Salomon, Rémi, Saunier, Sophie, Antignac, Corinne, Jeanpierre, Cécile, Heidet, Laurence, Morinière, Vincent, Henry, Charline, De Tomasi, Lara, Reilly, Madeline Louise, Humbert, Camille, Alibeu, Olivier, Fourrage, Cécile, Bole-Feysot, Christine, Nitschké, Patrick, Tores, Frédéric, Bras, Marc, Jeanpierre, Marc, Pietrement, Christine, Gaillard, Dominique, Gonzales, Marie, Novo, Robert, Schaefer, Elise, Roume, Joëlle, Martinovic, Jelena, Malan, Valérie, Salomon, Rémi, Saunier, Sophie, Antignac, Corinne, Jeanpierre, Cécile |
| author_sort | heidet, laurence |
| container_issue | 10 |
| container_start_page | 2901 |
| container_title | Journal of the American Society of Nephrology |
| container_volume | 28 |
| description | <jats:p>Congenital anomalies of the kidney and urinary tract (CAKUT) occur in three to six of 1000 live births, represent about 20% of the prenatally detected anomalies, and constitute the main cause of CKD in children. These disorders are phenotypically and genetically heterogeneous. Monogenic causes of CAKUT in humans and mice have been identified. However, despite high-throughput sequencing studies, the cause of the disease remains unknown in most patients, and several studies support more complex inheritance and the role of environmental factors and/or epigenetics in the pathophysiology of CAKUT. Here, we report the targeted exome sequencing of 330 genes, including genes known to be involved in CAKUT and candidate genes, in a cohort of 204 unrelated patients with CAKUT; 45% of the patients were severe fetal cases. We identified pathogenic mutations in 36 of 204 (17.6%) patients. These mutations included five <jats:italic toggle="yes">de novo</jats:italic> heterozygous loss of function mutations/deletions in the PBX homeobox 1 gene (<jats:italic toggle="yes">PBX1</jats:italic>), a gene known to have a crucial role in kidney development. In contrast, the frequency of <jats:italic toggle="yes">SOX17</jats:italic> and <jats:italic toggle="yes">DSTYK</jats:italic> variants recently reported as pathogenic in CAKUT did not indicate causality. These findings suggest that <jats:italic toggle="yes">PBX1</jats:italic> is involved in monogenic CAKUT in humans and call into question the role of some gene variants recently reported as pathogenic in CAKUT. Targeted exome sequencing also proved to be an efficient and cost-effective strategy to identify pathogenic mutations and deletions in known CAKUT genes.</jats:p> |
| doi_str_mv | 10.1681/asn.2017010043 |
| facet_avail | Online, Free |
| finc_class_facet | Medizin |
| format | ElectronicArticle |
| format_de105 | Article, E-Article |
| format_de14 | Article, E-Article |
| format_de15 | Article, E-Article |
| format_de520 | Article, E-Article |
| format_de540 | Article, E-Article |
| format_dech1 | Article, E-Article |
| format_ded117 | Article, E-Article |
| format_degla1 | E-Article |
| format_del152 | Buch |
| format_del189 | Article, E-Article |
| format_dezi4 | Article |
| format_dezwi2 | Article, E-Article |
| format_finc | Article, E-Article |
| format_nrw | Article, E-Article |
| geogr_code | not assigned |
| geogr_code_person | not assigned |
| id | ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTY4MS9hc24uMjAxNzAxMDA0Mw |
| imprint | Ovid Technologies (Wolters Kluwer Health), 2017 |
| imprint_str_mv | Ovid Technologies (Wolters Kluwer Health), 2017 |
| institution | DE-105, DE-14, DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1 |
| issn | 1046-6673, 1533-3450 |
| issn_str_mv | 1046-6673, 1533-3450 |
| language | English |
| last_indexed | 2024-03-01T16:15:11.424Z |
| match_str | heidet2017targetedexomesequencingidentifiespbx1asinvolvedinmonogeniccongenitalanomaliesofthekidneyandurinarytract |
| mega_collection | Ovid Technologies (Wolters Kluwer Health) (CrossRef) |
| physical | 2901-2914 |
| publishDate | 2017 |
| publishDateSort | 2017 |
| publisher | Ovid Technologies (Wolters Kluwer Health) |
| record_format | ai |
| recordtype | ai |
| series | Journal of the American Society of Nephrology |
| source_id | 49 |
| spelling | Heidet, Laurence Morinière, Vincent Henry, Charline De Tomasi, Lara Reilly, Madeline Louise Humbert, Camille Alibeu, Olivier Fourrage, Cécile Bole-Feysot, Christine Nitschké, Patrick Tores, Frédéric Bras, Marc Jeanpierre, Marc Pietrement, Christine Gaillard, Dominique Gonzales, Marie Novo, Robert Schaefer, Elise Roume, Joëlle Martinovic, Jelena Malan, Valérie Salomon, Rémi Saunier, Sophie Antignac, Corinne Jeanpierre, Cécile 1046-6673 1533-3450 Ovid Technologies (Wolters Kluwer Health) Nephrology General Medicine http://dx.doi.org/10.1681/asn.2017010043 <jats:p>Congenital anomalies of the kidney and urinary tract (CAKUT) occur in three to six of 1000 live births, represent about 20% of the prenatally detected anomalies, and constitute the main cause of CKD in children. These disorders are phenotypically and genetically heterogeneous. Monogenic causes of CAKUT in humans and mice have been identified. However, despite high-throughput sequencing studies, the cause of the disease remains unknown in most patients, and several studies support more complex inheritance and the role of environmental factors and/or epigenetics in the pathophysiology of CAKUT. Here, we report the targeted exome sequencing of 330 genes, including genes known to be involved in CAKUT and candidate genes, in a cohort of 204 unrelated patients with CAKUT; 45% of the patients were severe fetal cases. We identified pathogenic mutations in 36 of 204 (17.6%) patients. These mutations included five <jats:italic toggle="yes">de novo</jats:italic> heterozygous loss of function mutations/deletions in the PBX homeobox 1 gene (<jats:italic toggle="yes">PBX1</jats:italic>), a gene known to have a crucial role in kidney development. In contrast, the frequency of <jats:italic toggle="yes">SOX17</jats:italic> and <jats:italic toggle="yes">DSTYK</jats:italic> variants recently reported as pathogenic in CAKUT did not indicate causality. These findings suggest that <jats:italic toggle="yes">PBX1</jats:italic> is involved in monogenic CAKUT in humans and call into question the role of some gene variants recently reported as pathogenic in CAKUT. Targeted exome sequencing also proved to be an efficient and cost-effective strategy to identify pathogenic mutations and deletions in known CAKUT genes.</jats:p> Targeted Exome Sequencing Identifies PBX1 as Involved in Monogenic Congenital Anomalies of the Kidney and Urinary Tract Journal of the American Society of Nephrology |
| spellingShingle | Heidet, Laurence, Morinière, Vincent, Henry, Charline, De Tomasi, Lara, Reilly, Madeline Louise, Humbert, Camille, Alibeu, Olivier, Fourrage, Cécile, Bole-Feysot, Christine, Nitschké, Patrick, Tores, Frédéric, Bras, Marc, Jeanpierre, Marc, Pietrement, Christine, Gaillard, Dominique, Gonzales, Marie, Novo, Robert, Schaefer, Elise, Roume, Joëlle, Martinovic, Jelena, Malan, Valérie, Salomon, Rémi, Saunier, Sophie, Antignac, Corinne, Jeanpierre, Cécile, Journal of the American Society of Nephrology, Targeted Exome Sequencing Identifies PBX1 as Involved in Monogenic Congenital Anomalies of the Kidney and Urinary Tract, Nephrology, General Medicine |
| title | Targeted Exome Sequencing Identifies PBX1 as Involved in Monogenic Congenital Anomalies of the Kidney and Urinary Tract |
| title_full | Targeted Exome Sequencing Identifies PBX1 as Involved in Monogenic Congenital Anomalies of the Kidney and Urinary Tract |
| title_fullStr | Targeted Exome Sequencing Identifies PBX1 as Involved in Monogenic Congenital Anomalies of the Kidney and Urinary Tract |
| title_full_unstemmed | Targeted Exome Sequencing Identifies PBX1 as Involved in Monogenic Congenital Anomalies of the Kidney and Urinary Tract |
| title_short | Targeted Exome Sequencing Identifies PBX1 as Involved in Monogenic Congenital Anomalies of the Kidney and Urinary Tract |
| title_sort | targeted exome sequencing identifies pbx1 as involved in monogenic congenital anomalies of the kidney and urinary tract |
| title_unstemmed | Targeted Exome Sequencing Identifies PBX1 as Involved in Monogenic Congenital Anomalies of the Kidney and Urinary Tract |
| topic | Nephrology, General Medicine |
| url | http://dx.doi.org/10.1681/asn.2017010043 |