Renal and Extrarenal Phenotypes in Patients With HNF1B Variants and Chromosome 17q12 Microdeletions
Chronic kidney disease; Genotype-phenotype correlation; Outcome
| Authors: | ; ; ; ; ; ; |
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| Format: | Article |
| Status: | Published version |
| Publication date: | 2024 |
| Country: | España |
| Institution: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repository: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:11351/12166 |
| Online Access: | https://hdl.handle.net/11351/12166 http://hdl.handle.net/11351/12166 |
| Access Level: | Open access |
| Keyword: | Anomalies cromosòmiques Ronyons - Malalties - Aspectes genètics Fenotip DISEASES::Male Urogenital Diseases::Urologic Diseases::Kidney Diseases Other subheadings::Other subheadings::Other subheadings::/genetics PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation PHENOMENA AND PROCESSES::Genetic Phenomena::Phenotype ENFERMEDADES::enfermedades urogenitales masculinas::enfermedades urológicas::enfermedades renales Otros calificadores::Otros calificadores::Otros calificadores::/genética FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación FENÓMENOS Y PROCESOS::fenómenos genéticos::fenotipo |
| _version_ | 1878729055516229632 |
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| author | Buffin-Meyer, Bénédicte |
| author2 | Richard, Juliette Guigonis, Vincent Weber, Stefanie König, Jens Christian Heidet, Laurence Cruz Gual, Alejandro |
| author2_role | author author author author author author |
| author_browse | Buffin-Meyer, Bénédicte Cruz Gual, Alejandro Guigonis, Vincent Heidet, Laurence König, Jens Christian Richard, Juliette Weber, Stefanie |
| author_facet | Buffin-Meyer, Bénédicte Richard, Juliette Guigonis, Vincent Weber, Stefanie König, Jens Christian Heidet, Laurence Cruz Gual, Alejandro |
| author_role | author |
| collection | Recercat. Dipósit de la Recerca de Catalunya |
| description | Chronic kidney disease; Genotype-phenotype correlation; Outcome |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_00a3dd32d2609b84a56dd54dd5bba661 |
| institution | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| instname_str | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:recercat.cat:11351/12166 |
| publishDate | 2024 |
| publishDateSort | 2024 |
| publisher | Elsevier |
| publisherStr | Elsevier |
| reponame_str | Recercat. Dipósit de la Recerca de Catalunya |
| spelling | Renal and Extrarenal Phenotypes in Patients With HNF1B Variants and Chromosome 17q12 Microdeletions Buffin-Meyer, Bénédicte Richard, Juliette Guigonis, Vincent Weber, Stefanie König, Jens Christian Heidet, Laurence Cruz Gual, Alejandro Anomalies cromosòmiques Ronyons - Malalties - Aspectes genètics Fenotip DISEASES::Male Urogenital Diseases::Urologic Diseases::Kidney Diseases Other subheadings::Other subheadings::Other subheadings::/genetics PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation PHENOMENA AND PROCESSES::Genetic Phenomena::Phenotype ENFERMEDADES::enfermedades urogenitales masculinas::enfermedades urológicas::enfermedades renales Otros calificadores::Otros calificadores::Otros calificadores::/genética FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación FENÓMENOS Y PROCESOS::fenómenos genéticos::fenotipo Chronic kidney disease; Genotype-phenotype correlation; Outcome Enfermedad renal crónica; Correlación genotipo-fenotipo; Resultado Malaltia renal crònica; Correlació genotip-fenotip; Resultat Introduction Hepatocyte nuclear factor 1-beta (HNF1B) gene variants or the chromosome 17q12 deletion (17q12del) represent the most common monogenic cause of developmental kidney disease. Although neurodevelopmental disorders have been associated with the 17q12del, specific genotype-phenotype associations with respect to kidney function evolution have not yet been fully defined. Here, we aimed to determine whether 17q12del or specific HNF1B variants were associated with kidney survival in a large patient population with HNF1B disease. Methods This was a retrospective observational study involving 521 patients with HNF1B disease from 14 countries using the European Reference Network for rare kidney diseases with detailed information on the HNF1B genotype (HNF1B variants or the 17q12del). Median follow-up time was 11 years with 6 visits per patient. The primary end point was progression to chronic kidney disease (CKD) stage 3 (estimated glomerular filtration rate [eGFR] < 60 ml/min per 1.73 m2). Secondary end points were the development of hypomagnesemia or extrarenal disorders, including hyperuricemia and hyperglycemia. Results Progression toward CKD stage 3 was significantly delayed in patients with the 17q12del compared to patients with HNF1B variants (hazard ratio [HR]: 0.29, 95% confidence interval [CI]: 0.19–0.44, P < 0.001). Progression toward CKD stage 3 was also significantly delayed when HNF1B variants involved the HNF1B Pit-1, Oct-1, and Unc-86 homeodomain (POUh) DNA-binding and transactivation domains rather than the POU-specific domain (POUs) DNA-binding domain (HR: 0.15 [95% CI: 0.06–0.37), P < 0.001 and HR: 0.25 (95% CI: 0.11–0.57), P = 0.001, respectively). Finally, the 17q12del was positively associated with hypomagnesemia and negatively associated with hyperuricemia, but not with hyperglycemia. Conclusion Patients with the 17q12del display a significantly better kidney survival than patients with other HNF1B variants; and for the latter, variants in the POUs DNA-binding domain lead to the poorest kidney survival. These are clinically relevant HNF1B kidney genotype-phenotype correlations that inform genetic counseling. NEOCYST is funded by the German Federal Ministry of Education and Research–grant code 01GM1515A. This project has been supported by the European Reference Network for rare kidney diseases (ERKNet). ERKNet is funded by the European Union within the framework of the EU4Health Programme (grant No.HS g-23-49). Elsevier https://hdl.handle.net/11351/12166 http://hdl.handle.net/11351/12166 |
| spellingShingle | Renal and Extrarenal Phenotypes in Patients With HNF1B Variants and Chromosome 17q12 Microdeletions Buffin-Meyer, Bénédicte Anomalies cromosòmiques Ronyons - Malalties - Aspectes genètics Fenotip DISEASES::Male Urogenital Diseases::Urologic Diseases::Kidney Diseases Other subheadings::Other subheadings::Other subheadings::/genetics PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation PHENOMENA AND PROCESSES::Genetic Phenomena::Phenotype ENFERMEDADES::enfermedades urogenitales masculinas::enfermedades urológicas::enfermedades renales Otros calificadores::Otros calificadores::Otros calificadores::/genética FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación FENÓMENOS Y PROCESOS::fenómenos genéticos::fenotipo |
| status_str | publishedVersion |
| title | Renal and Extrarenal Phenotypes in Patients With HNF1B Variants and Chromosome 17q12 Microdeletions |
| title_full | Renal and Extrarenal Phenotypes in Patients With HNF1B Variants and Chromosome 17q12 Microdeletions |
| title_fullStr | Renal and Extrarenal Phenotypes in Patients With HNF1B Variants and Chromosome 17q12 Microdeletions |
| title_full_unstemmed | Renal and Extrarenal Phenotypes in Patients With HNF1B Variants and Chromosome 17q12 Microdeletions |
| title_short | Renal and Extrarenal Phenotypes in Patients With HNF1B Variants and Chromosome 17q12 Microdeletions |
| title_sort | Renal and Extrarenal Phenotypes in Patients With HNF1B Variants and Chromosome 17q12 Microdeletions |
| topic | Anomalies cromosòmiques Ronyons - Malalties - Aspectes genètics Fenotip DISEASES::Male Urogenital Diseases::Urologic Diseases::Kidney Diseases Other subheadings::Other subheadings::Other subheadings::/genetics PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation PHENOMENA AND PROCESSES::Genetic Phenomena::Phenotype ENFERMEDADES::enfermedades urogenitales masculinas::enfermedades urológicas::enfermedades renales Otros calificadores::Otros calificadores::Otros calificadores::/genética FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación FENÓMENOS Y PROCESOS::fenómenos genéticos::fenotipo |
| topic_facet | Anomalies cromosòmiques Ronyons - Malalties - Aspectes genètics Fenotip DISEASES::Male Urogenital Diseases::Urologic Diseases::Kidney Diseases Other subheadings::Other subheadings::Other subheadings::/genetics PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation PHENOMENA AND PROCESSES::Genetic Phenomena::Phenotype ENFERMEDADES::enfermedades urogenitales masculinas::enfermedades urológicas::enfermedades renales Otros calificadores::Otros calificadores::Otros calificadores::/genética FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación FENÓMENOS Y PROCESOS::fenómenos genéticos::fenotipo |
| url | https://hdl.handle.net/11351/12166 http://hdl.handle.net/11351/12166 |