Renal and Extrarenal Phenotypes in Patients With HNF1B Variants and Chromosome 17q12 Microdeletions

Bénédicte Buffin-Meyer; Juliette Richard; Vincent Guigonis; Stefanie Weber; Jens König; Laurence Heidet; Nabila Moussaoui; Jeanne-Pierrette Vu; Stanislas Faguer; Audrey Casemayou; Richa Prakash; Véronique Baudouin; Julien Hogan; Demi Alexandrou; Detlef Bockenhauer; Justine Bacchetta; Bruno Ranchin; Stepanka Pruhova; Jakub Zieg; Annie Lahoche; Christine Okorn; Violetta Antal-Kónya; Denis Morin; Francesca Becherucci; Sandra Habbig; Max C. Liebau; Mathilde Mauras; Tom Nijenhuis; Brigitte Llanas; Djalila Mekahli; Julia Thumfart; Burkhard Tönshoff; Laura Massella; Philippe Eckart; Sylvie Cloarec; Alejandro Cruz; Ludwig Patzer; Gwenaelle Roussey; Isabelle Vrillon; Olivier Dunand; Lucie Bessenay; Francesca Taroni; Marcin Zaniew; Ferielle Louillet; Carsten Bergmann; Franz Schaefer; Albertien M. van Eerde; Joost P. Schanstra; Stéphane Decramer; Gema Ariceta; Elisa Benetti; Marcus R. Benz; Anna Bjerre; Bernard R. Boudailliez; Antonia Bouts; Jens Drube; Ann Christin Gjerstad; Augustina Jankauskiene; Eszter Jávorszky; Nadine Jay; Martin Kirschstein; Nataša Marčun Varda; Olivier Niel; François Nobili; Christine Pietrement; Dovile Ruzgiene; Raphael Schild; Hagen Staude; Kálmán Tory; Michel Tsimaratos; Ulrike Walden; Hildegard Zappel; HNF1B variant study group

doi:10.1016/j.ekir.2024.05.007

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Renal and Extrarenal Phenotypes in Patients With HNF1B Variants and Chromosome 17q12 Microdeletions

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Renal and Extrarenal Phenotypes in Patients With HNF1B Variants and Chromosome 17q12 Microdeletions

Bénédicte Buffin-Meyer, Juliette Richard, Vincent Guigonis, Stefanie Weber, Jens König, Laurence Heidet, Nabila Moussaoui, Jeanne-Pierrette Vu, Stanislas Faguer, Audrey Casemayou, …

Kidney international reports, Vol.9(8), pp.2514-2526

08/2024

DOI: https://doi.org/10.1016/j.ekir.2024.05.007

PMID: 39156164

Résumé

chronic kidney disease

genotype-phenotype correlation

HNF1B disease

outcome

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. 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. 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. 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. [Display omitted]

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Titre: Renal and Extrarenal Phenotypes in Patients With HNF1B Variants and Chromosome 17q12 Microdeletions
Créateurs - sans rôle: Bénédicte Buffin-Meyer - National Institute of Health and Medical Research (INSERM), UMR 1297, Institute of Cardiovascular and Metabolic Disease, Toulouse, France
Juliette Richard - Department of Pediatric Internal Medicine, Rheumatology and Nephrology, Toulouse University Hospital, Toulouse, France
Vincent Guigonis - Department of Pediatrics, Hôpital Mère-Enfant, University Hospital of Limoges, Limoges, France
Stefanie Weber - Pediatric Nephrology, University Children's Hospital Marburg, Marburg, Germany
Jens König - Department of General Pediatrics, University Children's Hospital, Münster, Germany
Laurence Heidet - APHP, Service de Néphrologie Pédiatrique, Hôpital Universitaire Necker-Enfants malades, Paris, France
Nabila Moussaoui - National Institute of Health and Medical Research (INSERM), UMR 1297, Institute of Cardiovascular and Metabolic Disease, Toulouse, France
Jeanne-Pierrette Vu - National Institute of Health and Medical Research (INSERM), UMR 1297, Institute of Cardiovascular and Metabolic Disease, Toulouse, France
Stanislas Faguer - National Institute of Health and Medical Research (INSERM), UMR 1297, Institute of Cardiovascular and Metabolic Disease, Toulouse, France
Audrey Casemayou - National Institute of Health and Medical Research (INSERM), UMR 1297, Institute of Cardiovascular and Metabolic Disease, Toulouse, France
Richa Prakash - APHP, Service de Néphrologie Pédiatrique, Hôpital Universitaire Necker-Enfants malades, Paris, France
Véronique Baudouin - Nephrology Department, Robert Debré Hospital, APHP Nord, Paris University, Paris, France
Julien Hogan - Nephrology Department, Robert Debré Hospital, APHP Nord, Paris University, Paris, France
Demi Alexandrou - University College London Medical School, London, UK
Detlef Bockenhauer - University College London, Department of Renal Medicine, London, UK
Justine Bacchetta - Hôpital Femme Mère Enfant
Bruno Ranchin - Centre de Référence des Maladies Rénales Rares, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France
Stepanka Pruhova - Department of Pediatrics, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic
Jakub Zieg - Department of Pediatrics, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic
Annie Lahoche - Hôpital Jeanne de Flandre
Christine Okorn - Department of Pediatrics II, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany
Violetta Antal-Kónya - MTA-SE Lendület Nephrogenetic Laboratory, Budapest, Hungary
Denis Morin - Néphrologie Pédiatrique, CHU de Montpellier, Montpellier, France
Francesca Becherucci - Nephrology and Dialysis Unit, Meyer Children’s Hospital IRCCS, Florence, Italy
Sandra Habbig - Department of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
Max C. Liebau - University Hospital Cologne
Mathilde Mauras - Department of Pediatrics, Hôpital Nord, CHU de Saint-Etienne, Saint-Etienne, France
Tom Nijenhuis - Radboud University Medical Center
Brigitte Llanas - Unité de Néphrologie Pédiatrique, Hôpital Pellegrin-Enfants, CHU de Bordeaux, Centre de Références des Maladies rénales rares du Sud-Ouest (SORARE), Bordeaux, France
Djalila Mekahli - Department of Pediatric Nephrology, University Hospitals, Leuven, Belgium
Julia Thumfart - Charité - Universitätsmedizin Berlin
Burkhard Tönshoff - Department of Pediatrics I, University Children's Hospital Heidelberg, Heidelberg, Germany
Laura Massella - Bambino Gesù Children's Hospital
Philippe Eckart - Department of Pediatrics, University Hospital of Caen, Caen, France
Sylvie Cloarec - Centre Hospitalier Universitaire de Tours
Alejandro Cruz - Pediatric Nephrology, University Hospital Vall d’Hebron, Barcelona, Spain
Ludwig Patzer - Krankenhaus St. Elisabeth und St. Barbara
Gwenaelle Roussey - Service des Maladies Chroniques de l'Enfant, Hopital Mère Enfant, CHU Nantes, Nantes, France
Isabelle Vrillon - Hôpital des Enfants
Olivier Dunand - Service de Néphrologie Pédiatrique, CHU Réunion site Félix GUYON, St Denis, Ile de La Réunion, France
Lucie Bessenay - Department of Pediatric Nephrology, Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand, France
Francesca Taroni - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Marcin Zaniew - University of Zielona Góra
Ferielle Louillet - Département de Pédiatrie, Unité de Néphrologie-Hémodialyse, CHU Charles Nicolle, Rouen, France
Carsten Bergmann - Medizinische Genetik Mainz, Limbach Genetics, Mainz, Germany
Franz Schaefer - Division of Pediatric Nephrology, Heidelberg University Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany
Albertien M. van Eerde - Department of Genetics, UMC Utrecht, Utrecht, The Netherlands
Joost P. Schanstra - National Institute of Health and Medical Research (INSERM), UMR 1297, Institute of Cardiovascular and Metabolic Disease, Toulouse, France
Stéphane Decramer - National Institute of Health and Medical Research (INSERM), UMR 1297, Institute of Cardiovascular and Metabolic Disease, Toulouse, France
Gema Ariceta
Elisa Benetti
Marcus R. Benz
Anna Bjerre
Bernard R. Boudailliez
Antonia Bouts
Jens Drube
Ann Christin Gjerstad
Augustina Jankauskiene
Eszter Jávorszky
Nadine Jay
Martin Kirschstein
Nataša Marčun Varda
Olivier Niel
François Nobili
Christine Pietrement
Dovile Ruzgiene
Raphael Schild
Hagen Staude
Kálmán Tory
Michel Tsimaratos
Ulrike Walden
Hildegard Zappel
HNF1B variant study group
Détails de publication: Kidney international reports, Vol.9(8), pp.2514-2526
Éditeur: Elsevier Inc
Nombre de pages: 13
Identifiants: 99162983209311
Unité académique: Institut de Génomique Fonctionnelle - IGF
Langue: English
Type de ressource: Journal article