Search

Your search keyword '"Françoise Broux"' showing total 10 results
Start Over Author "Françoise Broux" Topic medicine.disease
10 results on '"Françoise Broux"'

1. Renal Prognosis in Children With Tubulointerstitial Nephritis and Uveitis Syndrome

Author

Corentin Tanne, François Nobili, Christine Pietrement, Emma Allain-Launay, Olivia Boyer, Claire Duflos, Annie Lahoche, Guylhène Bourdat-Michel, Sylvie Cloarec, Ariane Zaloszyc, Lise Allard, Agnès Chevalier, Djamal Djeddi, Tim Ulinski, Stéphane Decramer, Olivier Dunand, Julien Hogan, Justine Bacchetta, Marc Fila, Camille Faudeux, Stéphanie Clavé, Denis Morin, Isabelle Vrillon, Françoise Broux, Sophie Taque, Herrada, Anthony, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Assistance Publique - Hôpitaux de Marseille (APHM), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), AP-HP Hôpital universitaire Robert-Debré [Paris], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Rouen, Normandie Université (NU), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), CHU Bordeaux [Bordeaux], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Grenoble, CHU Amiens-Picardie, Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Centre Hospitalier Universitaire de Nice (CHU Nice), Service de pédiatrie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Pontchaillou [Rennes], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Strasbourg, Institut de Génomique Fonctionnelle (IGF), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Pediatrics, medicine.medical_specialty, Tubulointerstitial nephritis and uveitis, Renal function, tubulointerstitial nephritis and uveitis syndrome, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Asymptomatic, Dobrin’s syndrome, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, Clinical Research, medicine, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, business.industry, Retrospective cohort study, chronic kidney failure, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, pediatric, Nephrology, Dobrin's syndrome, Cohort, outcome, medicine.symptom, business, Uveitis, Kidney disease, Rare disease
Abstract

International audience; Introduction: Tubulointerstitial nephritis (TIN) and uveitis (TINU) syndrome is a rare disease. The renal prognosis is generally thought to be better in children with TINU syndrome than in adults. However, data are scarce. We aimed to investigate the long-term renal prognosis in a French cohort of children with TINU syndrome.Methods: We performed a national retrospective study including 23 French pediatric nephrology centers enrolling patients with TINU syndrome diagnosed between January 2000 and December 2018.Results: A total of 46 patients were included (52% female, median age 13.8 years). At diagnosis of TIN, the median estimated glomerular filtration rate (eGFR) was 30.6 ml/min per 1.73 m2 (4.9-62.8). The median time between diagnosis of uveitis and TIN was 0.4 months (-4.1; +17.1). All patients had anterior uveitis, but 12 (29%) were asymptomatic. Nearly all patients (44 of 46) received steroid treatment, and 12 patients (26%) received a second-line therapy. At last follow-up (median 2.8 years), the median eGFR was 87.5 ml/min per 1.73 m2 (60.3-152.7) and

Published
2021
Full Text
View/download PDF

2. Efficacy and safety of intravenous immunoglobulin with rituximab versus rituximab alone in childhood-onset steroid-dependent and frequently relapsing nephrotic syndrome: protocol for a multicentre randomised controlled trial

Author

Julien Hogan, Lucie Bessenay, Sylvie Cloarec, Stéphanie Tellier, Annie Lahoche, Camille Faudeux, Françoise Broux, Aubriana Perez, Djamal Djeddi, Claire Dossier, Isabelle Vrillon, Christine Pietrement, François Nobili, Jérôme Harambat, Anne Jolivot, Emmanuelle Plaisier, Georges Deschênes, S. Guilmin-Crépon, Olivia Boyer, Vincent Audard, Tim Ulinski, Véronique Baudouin, Philippe Eckart, Denis Morin, Anne-Laure Sellier-Leclerc, Gwenaëlle Roussey-Kesler, Vincent Guigonis, Hôpital Robert Debré, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Henri Mondor, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), and Université Sorbonne Paris Cité (USPC)

Subjects
Nephrology, Pediatrics, Nephrotic Syndrome, 030204 cardiovascular system & hematology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, LEHA, law.invention, 0302 clinical medicine, Superiority Trial, Randomized controlled trial, Quality of life, law, Recurrence, hemic and lymphatic diseases, Multicenter Studies as Topic, media_common, Randomized Controlled Trials as Topic, Renal Medicine, Immunoglobulins, Intravenous, Glomerulonephritis, General Medicine, 3. Good health, Treatment Outcome, Medicine, Rituximab, Steroids, medicine.drug, Drug, medicine.medical_specialty, media_common.quotation_subject, nephrology, 03 medical and health sciences, Internal medicine, medicine, Humans, 030203 arthritis & rheumatology, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, business.industry, paediatric nephrology, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, medicine.disease, Quality of Life, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neoplasm Recurrence, Local, business, Nephrotic syndrome, glomerulonephritis
Abstract

IntroductionGuidelines for the treatment of steroid-dependent nephrotic syndrome (SDNS) and frequently relapsing nephrotic syndrome (FRNS) are lacking. Given the substantial impact of SDNS/FRNS on quality of life, strategies aiming to provide long-term remission while minimising treatment side effects are needed. Several studies confirm that rituximab is effective in preventing early relapses in SDNS/FRNS; however, the long-term relapse rate remains high (~70% at 2 years). This trial will assess the association of intravenous immunoglobulins (IVIgs) to rituximab in patients with SDNS/FRNS and inform clinicians on whether IVIg’s immunomodulatory properties can alter the course of the disease and reduce the use of immunosuppressive drugs and their side effects.Methods and analysisWe conduct an open-label multicentre, randomised, parallel group in a 1:1 ratio, controlled, superiority trial to assess the safety and efficacy of a single infusion of rituximab followed by IVIg compared with rituximab alone in childhood-onset FRNS/SDNS. The primary outcome is the occurrence of first relapse within 24 months. Patients are allocated to receive either rituximab alone (375 mg/m²) or rituximab followed by IVIg, which includes an initial Ig dose of 2 g/kg, followed by 1.5 g/kg injections once a month for the following 5 months (maximum dose: 100 g).Ethics and disseminationThe study has been approved by the ethics committee (Comité de Protection des Personnes) of Ouest I and authorised by the French drug regulatory agency (Agence Nationale de Sécurité du Médicament et des Produits de Santé). Results of the primary study and the secondary aims will be disseminated through peer-reviewed publications.Trial registration numberNCT03560011.

Published
2020
Full Text
View/download PDF

3. Metabolic causes of nonimmune hydrops fetalis: A next-generation sequencing panel as a first-line investigation

Author

Annie Laquerrière, Bénédicte Sudrié-Arnaud, Raphaël Lanos, Laetitia Trestard, Ferielle Louillet, Sophie Coutant, Florent Marguet, Stéphane Marret, Abdellah Tebani, Sophie Patrier, Soumeya Bekri, Eric Verspyck, Myriam Vezain, Foudil Lamari, Pascal Chambon, Maria Fuller, Hélène Dranguet, Françoise Broux, Anne-Claire Brehin, Isabelle Tournier, Françoise Charbonnier, Jelena Martinovic, Laboratoire de biochimie générale [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre hospitalier universitaire de Rouen, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Anatomie et Cytologie Pathologique [CHU Rouen], Normandie Université (NU), Laboratoire Histologie Embryologie Cytogénétique [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de pédiatrie néonatale et réanimation - neuropédiatrie [CHU Rouen], Normandie Université (NU)-Normandie Université (NU)-Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), SA Pathology [Adelaide, SA, Australia], Service de Biochimie Métabolique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Clinique du Belvédère, Service de gynécologie et obstétrique [CHU Rouen], and Département de Pathologie [CHU Rouen]

Subjects
Adult, Polyhydramnios, 0301 basic medicine, Amniotic fluid, Clinical Biochemistry, Prenatal diagnosis, Genomics, Inborn errors of metabolism, Disease, 030105 genetics & heredity, Bioinformatics, Biochemistry, Inherited metabolic diseases, Young Adult, 03 medical and health sciences, Pregnancy, Hydrops fetalis, medicine, Humans, Non-immune hydrops fetalis, Retrospective Studies, [SDV.GEN]Life Sciences [q-bio]/Genetics, business.industry, Precision medicine, Biochemistry (medical), Computational Biology, Barth syndrome, Retrospective cohort study, Sequence Analysis, DNA, General Medicine, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, 3. Good health, 030104 developmental biology, Next-generation sequencing, Female, business, Metabolism, Inborn Errors
Abstract

Purposes Hydrops fetalis is a life-threatening fetal condition, and 85% of all cases are classified as nonimmune hydrops fetalis (NIHF). Up to 15% of NIHF cases may be due to inborn errors of metabolism (IEM), but a large proportion of cases linked to metabolic disorders remains undiagnosed. This lack of diagnosis may be related to the limitations of conventional biological procedures, which involve sequential investigations and require multiple samples and steps. In addition, this approach is time consuming. We have developed a next-generation sequencing (NGS) panel to investigate metabolic causes of NIHF, ascites, and polyhydramnios associated to another fetal abnormality. Methods The hydrops fetalis (HydFet) panel was designed to cover the coding regions and flanking intronic sequences of 41 genes. A retrospective study of amniotic fluid samples from 40 subjects was conducted. A prospective study was subsequently initiated, and six samples were analyzed using the NGS panel. Results Five IEM diagnoses were made using the HydFet panel (Niemann-Pick type C (NPC), Barth syndrome, HNF1Β deficiency, GM1 gangliosidosis, and Gaucher disease). This analysis also allowed the identification of 8p sequence triplication in an additional case. Conclusion NGS combined with robust bioinformatics analyses is a useful tool for identifying the causative variants of NIHF. Subsequent functional characterization of the protein encoded by the altered gene and morphological studies may confirm the diagnosis. This paradigm shift allows a significant improvement of IEM diagnosis in NIHF.

Published
2018
Full Text
View/download PDF

4. Quality of life in adolescents with chronic kidney disease who initiate haemodialysis treatment

Author

Annie Lahoche, Isabelle Vrillon, Julie Berbis, Françoise Broux, Gwenaelle Roussey, Sylvie Cloarec, Jérôme Harambat, Michel Tsimaratos, Olivier Dunand, Mohamed Boucekine, Rémi Salomon, Soraya Menouer, Stéphanie Clavé, Bruno Ranchin, Arnaud Garnier, Marc Fila, Pascal Auquier, Georges Deschênes, Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Hôpital de la Timone [CHU - APHM] (TIMONE), Service de Néphrologie Rhumatologie Dermatologie, Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-HCL Groupement Hospitalier Est-Centre de référence Maladies Rénales Rares, Service de néphrologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Néphrologie, Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), CHU Toulouse [Toulouse], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Charles Nicolle [Rouen], Centre de Référence du Sud Ouest des Maladies Rénales Rares, CHU Toulouse [Toulouse]-Hôpital des Enfants, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital de Hautepierre [Strasbourg], Service de néphrologie et pédiatrie générale [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), French national research program for clinical research (PHRC), HCL Groupement Hospitalier Est-Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Centre de référence Maladies Rénales Rares, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Rouen, Normandie Université (NU)-Normandie Université (NU), CHU Trousseau [APHP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Adult, Male, Parents, Quality of life, Gerontology, medicine.medical_specialty, Coping (psychology), Medical staff, Multivariate analysis, Adolescent, Population, 030232 urology & nephrology, 030204 cardiovascular system & hematology, Adolescents, lcsh:RC870-923, End stage renal disease, End-stage renal disease, 03 medical and health sciences, Leisure Activities, 0302 clinical medicine, Renal Dialysis, Internal medicine, Adaptation, Psychological, Health care, medicine, Humans, Prospective Studies, Renal Insufficiency, Chronic, Child, education, Bayesian models, Initiating haemodialysis, Coping strategies, education.field_of_study, business.industry, Middle Aged, lcsh:Diseases of the genitourinary system. Urology, medicine.disease, 3. Good health, Nephrology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, France, Self Report, business, Research Article, Kidney disease
Abstract

Background To describe the quality of life of adolescents initiating haemodialysis, to determine the factors associated with quality of life, and to assess coping strategies and their impact on quality of life. Methods All adolescents initiating haemodialysis between September 2013 and July 2015 in French paediatric haemodialysis centres were included. Quality of life data were collected using the “Vécu et Santé Perçue de l’Adolescent et l’Enfant” questionnaire, and coping data were collected using the Kidcope questionnaire. Adolescent’s quality of life was compared with age- and sex-matched French control. Results Thirty-two adolescents were included. Their mean age was 13.9 ± 2.0 years. The quality of life score was lowest in leisure activities and highest in relationships with medical staff. Compared with the French control, index, energy-vitality, relationships with friends, leisure activities and physical well-being scores were significantly lower in haemodialysis population. In multivariate analyses, active coping was positively associated with quality of life and especially with energy-vitality, relationships with parents and teachers, and school performance. In contrast, avoidant and negative coping were negatively associated with energy-vitality, psychological well-being and body image for avoidant coping, and body image and relationships with medical staff for negative coping. Conclusions The quality of life of haemodialysis adolescents, and mainly the dimensions of leisure activities, physical well-being, relationships with friends and energy-vitality, were significantly altered compared to that of the French population. The impact of coping strategies on quality of life seems to be important. Given the importance of quality of life and coping strategies in adolescents with chronic disease, health care professionals should integrate these aspects into care management.

Published
2019
Full Text
View/download PDF

5. Familial Hypocalciuric Hypercalcemia Types 1 and 3 and Primary Hyperparathyroidism: Similarities and Differences

Author

Jean-Philippe Haymann, Delphine Vezzosi, Elisabeth Requeda, Agnès Linglart, Guy Lefort, Jean-Claude Souberbielle, Emmanuelle Dubosclard, Bernadette Lucas-Pouliquen, Jean-Marc Kuhn, Françoise Broux, Pascal Houillier, Lamisse Mansour-Hendili, Michel Polak, Sophie Ouzounian, Stéphanie Baron, Xavier Jeunemaitre, Christophe Simian, Sonia Beltran, Caroline Travers, Gérard Maruani, Xavier Debussche, Caroline Silve, Jean-Philippe Bertocchio, Catherine Cormier, Cyrielle Treard, Odile Camard, Celine Eid, Dominique Robier, Marie-Alice Macher, Sylvie Cloarec, Ivan Tack, Véronique Baudouin, Rosa Vargas-Poussou, and Soto Romuald Kiando

Subjects
Adult, Male, 0301 basic medicine, medicine.medical_specialty, Adaptor Protein Complex sigma Subunits, Genotype, endocrine system diseases, Endocrinology, Diabetes and Metabolism, DNA Mutational Analysis, Clinical Biochemistry, Adaptor Protein Complex 2, Parathyroid hormone, 030209 endocrinology & metabolism, Context (language use), Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Internal medicine, medicine, Humans, Hyperparathyroidism, Familial hypocalciuric hypercalcemia, Genetic heterogeneity, business.industry, Biochemistry (medical), Middle Aged, Hyperparathyroidism, Primary, medicine.disease, GTP-Binding Protein alpha Subunits, Urinary calcium, Cross-Sectional Studies, Phenotype, 030104 developmental biology, Parathyroid Hormone, Mutation, Calcium ion homeostasis, Hypercalcemia, Calcium, Female, business, Receptors, Calcium-Sensing, Primary hyperparathyroidism
Abstract

Familial hypocalciuric hypercalcemia (FHH) is a genetically heterogeneous condition resembling primary hyperparathyroidism (PHPT) but not curable by surgery; FHH types 1, 2, and 3 are due to loss-of-function mutations of the CASR, GNA11, or AP2S1 genes, respectively.This study aimed to compare the phenotypes of patients with genetically proven FHH types 1 or 3 or PHPT.This was a mutation analysis in a large cohort, a cross-sectional comparison of 52 patients with FHH type 1, 22 patients with FHH type 3, 60 with PHPT, and 24 normal adults.There were no interventions.Abnormalities of the CASR, GNA11, and AP2S1 genes, blood calcium, phosphate, and PTH concentrations, urinary calcium excretion were measured.In 133 families, we detected 101 mutations in the CASR gene, 68 of which were previously unknown, and in 19 families, the three recurrent AP2S1 mutations. No mutation was detected in the GNA11 gene. Patients with FHH type 3 had higher plasma calcium concentrations than patients with FHH type 1, despite having similar PTH concentrations and urinary calcium excretion. Renal tubular calcium reabsorption levels were higher in patients with FHH type 3 than in those with FHH type 1. Plasma calcium concentration was higher whereas PTH concentration and urinary calcium excretion were lower in FHH patients than in PHPT patients. In patients with FHH or PHPT, all data groups partially overlapped.In our population, AP2S1 mutations affect calcium homeostasis more severely than CASR mutations. Due to overlap, the risk of confusion between FHH and PHPT is high.

Published
2016
Full Text
View/download PDF

6. Comprehensive PKD1 and PKD2 Mutation Analysis in Prenatal Autosomal Dominant Polycystic Kidney Disease

Author

Annie Lahoche, Françoise Broux, Ferielle Louillet, Vincent Morinière, Olivia Boyer, Amélie Ryckenwaert, Hanitra Randrianaivo, Elodie Merieau, Said Lebbah, Stéphane Decramer, Marie-Pierre Audrézet, Djalila Mekahli, Sandrine Maestri, Laurence Heidet, Carine Abel, Christine Corbiere, Georges Deschênes, Claude Férec, Ines Ouertani, Rémi Salomon, Sylvie Cloarec, Emilie Cornec-Le Gall, Michel Fischbach, Véronique Baudouin, Chiara Visconti, Ariane Zaloszyc, Gwenaelle Roussey, and Lucie Bessenay

Subjects
Adult, Male, 0301 basic medicine, medicine.medical_specialty, TRPP Cation Channels, Adolescent, DNA Mutational Analysis, Autosomal dominant polycystic kidney disease, Mothers, Receptors, Cell Surface, Disease, urologic and male genital diseases, Ultrasonography, Prenatal, Fathers, Young Adult, 03 medical and health sciences, Internal medicine, Polycystic kidney disease, Humans, Medicine, Child, Aged, Hepatocyte Nuclear Factor 1-beta, Retrospective Studies, Cystic kidney, Genetics, PKD1, urogenital system, business.industry, Infant, General Medicine, Middle Aged, Polycystic Kidney, Autosomal Dominant, medicine.disease, HNF1B, female genital diseases and pregnancy complications, Pedigree, 030104 developmental biology, Endocrinology, Nephrology, Child, Preschool, Mutation, Mutation (genetic algorithm), Mutation testing, Kidney Failure, Chronic, Female, Brief Communications, business
Abstract

Prenatal forms of autosomal dominant polycystic kidney disease (ADPKD) are rare but can be recurrent in some families, suggesting a common genetic modifying background. Few patients have been reported carrying, in addition to the familial mutation, variation(s) in polycystic kidney disease 1 (PKD1) or HNF1 homeobox B (HNF1B), inherited from the unaffected parent, or biallelic polycystic kidney and hepatic disease 1 (PKHD1) mutations. To assess the frequency of additional variations in PKD1, PKD2, HNF1B, and PKHD1 associated with the familial PKD mutation in early ADPKD, these four genes were screened in 42 patients with early ADPKD in 41 families. Two patients were associated with de novo PKD1 mutations. Forty patients occurred in 39 families with known ADPKD and were associated with PKD1 mutation in 36 families and with PKD2 mutation in two families (no mutation identified in one family). Additional PKD variation(s) (inherited from the unaffected parent when tested) were identified in 15 of 42 patients (37.2%), whereas these variations were observed in 25 of 174 (14.4%, P=0.001) patients with adult ADPKD. No HNF1B variations or PKHD1 biallelic mutations were identified. These results suggest that, at least in some patients, the severity of the cystic disease is inversely correlated with the level of polycystin 1 function.

Published
2016
Full Text
View/download PDF

7. Prevalence of Novel MAGED2 Mutations in Antenatal Bartter Syndrome

Author

Amélie Ryckewaert, Nadine Jay, Aurélia Bertholet-Thomas, Gilles Morin, Georges Deschênes, Cyrielle Treard, Vincent Guigonis, Rémi Salomon, Denis Morin, Brigitte Llanas, Rosa Vargas-Poussou, Daniele Bruno, Stéphane Decramer, Djamal Djeddi, François Nobili, Anne Blanchard, Isabelle Vrillon, Tackwa Khalifeh, Christine Pietrement, Françoise Broux, Sophie Dreux, Isabelle Roncelin, Anne Legrand, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Toulouse [Toulouse], Service de Pédiatrie médicale [CHU Limoges], CHU Limoges, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre de Référence du Sud Ouest des Maladies Rénales Rares, CHU Toulouse [Toulouse]-Hôpital des Enfants, CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Amiens-Picardie, Service de pédiatrie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de néphrologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Investigation Clinique - Epidemiologie Clinique/essais Cliniques [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM), and École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)

Subjects
0301 basic medicine, Proband, Male, Pediatrics, Epidemiology, [SDV]Life Sciences [q-bio], DNA Mutational Analysis, 030232 urology & nephrology, Critical Care and Intensive Care Medicine, 0302 clinical medicine, Mutation Rate, Pregnancy, Prenatal Diagnosis, Prevalence, Missense mutation, Frameshift Mutation, X chromosome, Sequence Deletion, Sanger sequencing, education.field_of_study, Pregnancy Outcome, genetic renal disease, Adaptor Proteins, 3. Good health, Phenotype, Nephrology, Cohort, symbols, Female, France, Polyhydramnios, medicine.medical_specialty, X Chromosome, RNA Splicing, Population, Bartter syndrome, Frameshift mutation, 03 medical and health sciences, symbols.namesake, pediatric nephrology, Antigens, Neoplasm, medicine, Humans, Genetic Predisposition to Disease, Antigens, education, Adaptor Proteins, Signal Transducing, Retrospective Studies, Transplantation, business.industry, Signal Transducing, Bartter Syndrome, Original Articles, medicine.disease, 030104 developmental biology, Mutation, molecular genetics, Neoplasm, business
Abstract

International audience; BACKGROUND AND OBJECTIVES: Mutations in the MAGED2 gene, located on the X chromosome, have been recently detected in males with a transient form of antenatal Bartter syndrome or with idiopathic polyhydramnios. The aim of this study is to analyze the proportion of the population with mutations in this gene in a French cohort of patients with antenatal Bartter syndrome. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The French cohort of patients with antenatal Bartter syndrome encompasses 171 families. Mutations in genes responsible for types 1-4 have been detected in 75% of cases. In patients without identified genetic cause (n=42), transient antenatal Bartter syndrome was reported in 12 cases. We analyzed the MAGED2 gene in the entire cohort of negative cases by Sanger sequencing and retrospectively collected clinical data regarding pregnancy as well as the postnatal outcome for positive cases. RESULTS: We detected mutations in MAGED2 in 17 patients, including the 12 with transient antenatal Bartter syndrome, from 16 families. Fifteen different mutations were detected (one whole deletion, three frameshift, three splicing, three nonsense, two inframe deletions, and three missense); 13 of these mutations had not been previously described. Interestingly, two patients are females; in one of these patients our data are consistent with selective inactivation of chromosome X explaining the severity. The phenotypic presentation in our patients was variable and less severe than that of the originally described cases. CONCLUSIONS: MAGED2 mutations explained 9% of cases of antenatal Bartter syndrome in a French cohort, and accounted for 38% of patients without other characterized mutations and for 44% of male probands of negative cases. Our study confirmed previously published data and showed that females can be affected. As a result, this gene must be included in the screening of the most severe clinical form of Bartter syndrome.

Published
2018
Full Text
View/download PDF

8. Mycophenolate mofetil for steroid-dependent nephrotic syndrome: a phase II Bayesian trial

Author

Evelyne Jacqz-Aigrain, Georges Deschênes, Chantal Loirat, Jean-Luc André, Patrick Niaudet, Véronique Baudouin, Anne-Laure Lapeyraque, Françoise Broux, Stéphane Decramer, Albert Bensman, Corinne Alberti, and Mathilde Cailliez

Subjects
Male, medicine.medical_specialty, Nephrotic Syndrome, Adolescent, Cyclophosphamide, Urology, Pharmacokinetics, Prednisone, medicine, Humans, Prospective Studies, Child, Prospective cohort study, Maintenance dose, Cumulative dose, business.industry, Bayes Theorem, Mycophenolic Acid, medicine.disease, Surgery, Clinical trial, Nephrology, Area Under Curve, Child, Preschool, Pediatrics, Perinatology and Child Health, Female, business, Nephrotic syndrome, Immunosuppressive Agents, medicine.drug
Abstract

Mycophenolate mofetil (MMF) has emerged as a new therapeutic option in steroid-dependent nephrotic syndrome (SDNS). We conducted a phase II Bayesian trial of MMF in children with SDNS. Phase II trials, usually single-arm studies, investigate the effect of new treatments. Standard Fleming's procedure relies on observed results (relapse rate during the trial), whereas Bayesian approach combines observed results with prior information (expected relapse rate according to prior studies and clinical experience). All patients were required to have received prior alkylating-agent treatment. Sixty-seven percent of them had also received levamisole. Patients received MMF (1,200 mg/m(2)/day) and prednisone according to a defined schedule [reduction of alternate-day (e.o.d) dose to 50% of pre-MMF dose at 3 months, 25% at 6 months]. Twenty-four children (median age 6.0 years, 2.8-14.4) entered the study and 23 completed it. Bayesian analysis showed that adding four patients would not change significance of results, allowing stopping inclusions. Four patients relapsed during the first 6 months (estimated probability 17.6%, 95% credibility interval: 5.4-35.0%) and two at months 8 and 11.5. In the 19 patients free of relapse during the first 6 months, median (Q1-Q3) prednisone maintenance dose decreased from 25 (10-44) to 9 (7.5-11.2) mg/m(2) e.o.d (p0.001) and cumulative dose from 459 (382-689) to 264 (196-306) mg/m(2)/month (p0.001) before and on MMF respectively. Pre-MMF patient characteristics and MMF pharmacokinetics did not differ between patients with or without relapse. MMF reduces relapse rate and steroid dose in children with SDNS and should be proposed before cyclosporine and cyclophosphamide.

Published
2011
Full Text
View/download PDF

9. KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron

Author

Daniel Trujillano, Patrick Niaudet, Amélie Bonnefond, Xavier Jeunemaitre, Pascal Houillier, Olivier Sand, Mark J. Caulfield, Geneviève Beaurain, Stéphanie Miserey-Lenkei, Paul Landais, Robert J. Unwin, Georg Ehret, Chebel Mourani, Olivier Chabre, Vincent L.M. Esnault, Corinne Isnard Bagnis, Christophe Simian, Juliette Hadchouel, Patrick Bruneval, Stephan Ossowski, Béatrice Fiquet, Christelle Soukaseum, Hélène Louis-Dit-Picard, Christel Thauvin, Emmanuelle Vidal-Petiot, Julien Barc, Olena Pylypenko, Steven D. Soroka, Nabila Bouatia-Naji, Michel Delahousse, Philippe Froguel, Jean-Jacques Schott, Xavier Estivill, Jens Koenig, Chantal Mandet, Vincent Probst, Martin Konrad, Françoise Broux, Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Mécanismes moléculaires du transport intracellulaire, Compartimentation et dynamique cellulaires (CDC), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC), Epidemiology Unit, Addenbrooke's Hospital-Medical Research Council (MRC), Motilité structurale, Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Bioinformatique des Génomes et des Réseaux (BiGRe), Université libre de Bruxelles (ULB), Service Génétique, Union nationale des coopératives d’élevage et d’insémination animale (UNCEIA), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'endocrinologie, CHU Grenoble-Hôpital Michallon, Service de transplantation rénale, Hôpital Foch [Suresnes], Service de néphrologie, Centre Hospitalier Universitaire de Nice (CHU Nice), Pharmaceut, Med & Sci Affairs, Novartis, Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de néphrologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University Children's Hospital, Munster, Westfälische Wilhelms-Universität Münster (WWU), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), UFR de médecine (Université de Bourgogne), Université de Bourgogne (UB), Royal Free and University College Medical School, Center for Nephrology, Laboratoire de Recherche en Imagerie : Méthodes d'imagerie des Échanges transcapillaires (LRI - EA4062), Universitat Pompeu Fabra [Barcelona] (UPF), Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Ehret, Georg Benedikt, Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Néphrologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de recherche de l'institut du thorax (ITX-lab), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut Curie-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut Curie-Université Pierre et Marie Curie - Paris 6 (UPMC), Génomique Intégrative et Modélisation des Maladies Métaboliques (EGID), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Université Libre de Bruxelles [Bruxelles] (ULB), Union Nationale des Coopératives Agricoles d'Elevage et d'Insémination Animale, Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Génétique Médicale, Hopital, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), and Universitat Pompeu Fabra [Barcelona]

Subjects
Male, Carrier Proteins/genetics, Pseudohypoaldosteronism/genetics/metabolism/physiopathology, Pseudohypoaldosteronism, [SDV]Life Sciences [q-bio], Blood Pressure, 030204 cardiovascular system & hematology, Nephrons/metabolism, Kidney, 0302 clinical medicine, Missense mutation, Child, ComputingMilieux_MISCELLANEOUS, Genetics, ddc:616, Aged, 80 and over, 0303 health sciences, biology, Microfilament Proteins, Middle Aged, WNK1, Phenotype, Sodium Chloride Symporters, WNK4, Ubiquitin ligase, Female, Signal Transduction, Adult, medicine.medical_specialty, Adolescent, Blood Pressure/genetics, Ion Transport/genetics, Molecular Sequence Data, Polymorphism, Single Nucleotide, 03 medical and health sciences, Young Adult, Internal medicine, medicine, Humans, Amino Acid Sequence, Sodium Chloride Symporters/genetics/metabolism, 030304 developmental biology, Adaptor Proteins, Signal Transducing, Aged, Ion Transport, Base Sequence, urogenital system, Kidney metabolism, Nephrons, Sequence Analysis, DNA, medicine.disease, Kidney/metabolism, Endocrinology, Ion homeostasis, biology.protein, Carrier Proteins
Abstract

Familial hyperkalemic hypertension (FHHt) is a Mendelian form of arterial hypertension that is partially explained by mutations in WNK1 and WNK4 that lead to increased activity of the Na(+)-Cl(-) cotransporter (NCC) in the distal nephron. Using combined linkage analysis and whole-exome sequencing in two families, we identified KLHL3 as a third gene responsible for FHHt. Direct sequencing of 43 other affected individuals revealed 11 additional missense mutations that were associated with heterogeneous phenotypes and diverse modes of inheritance. Polymorphisms at KLHL3 were not associated with blood pressure. The KLHL3 protein belongs to the BTB-BACK-kelch family of actin-binding proteins that recruit substrates for Cullin3-based ubiquitin ligase complexes. KLHL3 is coexpressed with NCC and downregulates NCC expression at the cell surface. Our study establishes a role for KLHL3 as a new member of the complex signaling pathway regulating ion homeostasis in the distal nephron and indirectly blood pressure.

Published
2012
Full Text
View/download PDF

10. Phenotype-genotype correlation in antenatal and neonatal variants of Bartter syndrome

Author

Chantal Loirat, Olivia Boyer, Georges Deschênes, Mathilde Caillez, Anne Blanchard, Robert Novo, Rosa Vargas-Poussou, Patrick Niaudet, Pierre Cochat, Stéphane Decramer, Claude Guyot, Albert Bensman, Marie-Alice Macher, Karine Brochard, Xavier Jeunemaitre, Françoise Broux, and Denis Morin

Subjects
Male, Polyhydramnios, medicine.medical_specialty, Adolescent, Genotype, Turkey, Sodium-Potassium-Chloride Symporters, Deafness, Bartter syndrome, Gastroenterology, White People, Tubulopathy, Africa, Northern, Chloride Channels, Internal medicine, medicine, Humans, Africa, Central, Potassium Channels, Inwardly Rectifying, Child, Retrospective Studies, Solute Carrier Family 12, Member 1, Transplantation, CLCNKB, biology, business.industry, Bartter Syndrome, Infant, medicine.disease, Hypokalemia, Bartter's syndrome, Nephrocalcinosis, Endocrinology, Phenotype, Nephrology, Child, Preschool, Mutation, biology.protein, Hyperkalemia, Female, medicine.symptom, business, Kidney disease, Follow-Up Studies
Abstract

Background Ante/neonatal Bartter syndrome (BS) is a hereditary salt-losing tubulopathy due to mutations in genes encoding proteins involved in NaCl reabsorption in the thick ascending limb of Henle's loop. Our aim was to study the frequency, clinical characteristics and outcome of each genetic subtype. Methods Charts of 42 children with mutations in KCNJ1 (n = 19), SLC12A1 (n = 13) CLCNKB (n = 6) or BSND (n = 4) were retrospectively analysed. The median follow-up was 8.3 [0.4-18.0] years. Results We describe 24 new mutations: 10 in KCNJ1, 11 in SLC12A1 and 3 in CLCNKB. The onset of polyhydramnios, birth term, height and weight were similar for all groups; three patients had no history of polyhydramnios or premature birth and had CLCNKB mutations according to a less severe renal sodium wasting. Contrasting with these data, patients with CLCNKB had the lowest potassium (P = 0.006 versus KCNJ1 and P = 0.034 versus SLC12A1) and chloride plasma concentrations (P = 0.039 versus KCNJ1 and P = 0.024 versus SLC12A1) and the highest bicarbonataemia (P = 0.026 versus KCNJ1 and P = 0.014 versus SLC12A1). Deafness at diagnosis was constant in patients with BSND mutations; transient neonatal hyperkalaemia was present in two-thirds of the children with KCNJ1 mutations. Nephrocalcinosis was constant in KCNJ1 and SLC12A1 but not in BSND and CLCNKB patients. In most cases, water/electrolyte supplementation + indomethacin led to catch-up growth. Three patients developed chronic renal failure: one with KCNJ1 mutations during the second decade of age and two with CLCNKB and BSND mutations and without nephrocalcinosis during the first year of life. Conclusions We confirmed in a large cohort of ante/ neonatal BS that deafness, transient hyperkalaemia and severe hypokalaemic hypochloraemic alkalosis orientate molecular investigations to BSND, KCNJ1 and CLCNKB genes, respectively. Chronic renal failure is a rare event, associated in this cohort with three genotypes and not always associated with nephrocalcinosis.

Published
2008

Catalog

Books, media, physical & digital resources
See catalog results