2026-04-13T07:34:13Zhttps://recercat.cat/oai/requestoai:recercat.cat:11351/121662025-10-24T10:19:51Zcom_2072_378070com_2072_378040col_2072_378092
RECERCAT
author
Buffin-Meyer, Bénédicte
author
Richard, Juliette
author
Guigonis, Vincent
author
Weber, Stefanie
author
König, Jens Christian
author
Heidet, Laurence
author
Cruz Gual, Alejandro
2025-10-24T10:19:51Z
2025-10-24T10:19:51Z
2024-10-31T11:47:12Z2024-10-31T11:47:12Z2024-05-15
http://hdl.handle.net/11351/12166
Chronic kidney disease; Genotype-phenotype correlation; OutcomeEnfermedad renal crónica; Correlación genotipo-fenotipo; ResultadoMalaltia renal crònica; Correlació genotip-fenotip; ResultatIntroduction
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).
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess
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
Renal and Extrarenal Phenotypes in Patients With HNF1B Variants and Chromosome 17q12 Microdeletions
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion