Hélène Duval1,2, Laurence Michel-Calemard3, Marie Gonzales2,4, Philippe Loget2,5, Claire Beneteau6, Annie Buenerd2,7, Madeleine Joubert2,8, Marielee Denis-Musquer8, Alix Clemenson2,9, Anne-Laure Chesnais2,10, Sophie Blesson2,11, Isabelle De Pinieux12, Anne-Lise Delezoide2,13, Gheorghe Bonyhay14, Christine Bellanné-Chantelot14, Laurence Heidet15, Florence Dupré1, Sophie Collardeau-Frachon2,7,16. 1. Service de Pathologie, Centre Hospitalier Princesse Grace, Avenue Pasteur, Monaco. 2. SOFFOET, Société Française de Fœtopathologie, Lyon, Rennes, France. 3. Service d'Endocrinologie Moléculaire et Maladies Rares, Centre de Biologie et Pathologie Est, Bron, France. 4. Service de Génétique et d'Embryologie Médicales, Hôpital Armand Trousseau, APHP, UPMC, Paris, France. 5. Laboratoire d'Anatomie et de Cytologie Pathologiques, Hôpital Pontchaillou, Rennes, France. 6. Service de Génétique Médicale, Institut de Biologie, CHU de Nantes, Nantes, France. 7. Centre de Pathologie Est, Hôpital Femme-Mère-Enfant, Groupement Hospitalier Est, Hospices Civils de Lyon, Lyon, France. 8. Service d'Anatomie Pathologique, CHU Hôtel Dieu, Nantes, France. 9. Service d'Anatomie et Cytologie Pathologiques, CHU Saint-Etienne, Saint-Etienne, France. 10. Laboratoire d'Anatomie Pathologique-Neuropathologique, Hôpital de la Timone, Marseille, France. 11. Service de Génétique, Centre Olympes de Gouges, Hôpital Bretonneau, CHRU de Tours, Tours, France. 12. Cabinet de Pathologie Léonard de Vinci Chambray Les Tours, Tours, France. 13. Service de Biologie du Développement, Hôpital Robert Debré, APHP, Université Paris Diderot, Paris, France. 14. Département de Génétique, Université Pierre et Marie Curie, Paris, France. 15. Centre de Référence des Maladies Rénales Héréditaires de l'Enfant et de l'Adulte (MARHEA), AP-HP, Hôpital Necker, Paris, France. 16. Université Claude Bernard Lyon 1, Lyon, France.
Abstract
OBJECTIVES: To describe macroscopic and microscopic anomalies present in fetuses carrying hepatocyte nuclear factor-1 β mutation, their frequency, and genotype/phenotype correlations. METHODS: Clinical data, ultrasound findings, genetic studies, and autopsy reports of 20 fetal autopsies were analyzed. Histology was reviewed by two pathologists. RESULTS: Macroscopic findings were typically unilateral or bilateral renal enlargement and cortical cysts. Renal lesions were associated with congenital anomalies of the kidney and urinary tract in 25% of cases. Microscopic renal anomalies were dominated by glomerulocystic kidney and renal dysplasia. Extra-renal manifestations such as pancreatic hypoplasia (75%) and genital anomalies (68%) were only detected at autopsy. In 40% of cases, there was heterozygous deletion of the whole gene. There were de novo mutations in 40%. CONCLUSION: This study underlines the importance of considering hepatocyte nuclear factor-1 β mutations in fetuses with congenital anomalies of the kidney and urinary tract, especially when associated with pancreatic hypoplasia. No correlation between phenotype and genotype was found, highlighting high intra-familial variability in cases with inherited mutations.
OBJECTIVES: To describe macroscopic and microscopic anomalies present in fetuses carrying hepatocyte nuclear factor-1 β mutation, their frequency, and genotype/phenotype correlations. METHODS: Clinical data, ultrasound findings, genetic studies, and autopsy reports of 20 fetal autopsies were analyzed. Histology was reviewed by two pathologists. RESULTS: Macroscopic findings were typically unilateral or bilateral renal enlargement and cortical cysts. Renal lesions were associated with congenital anomalies of the kidney and urinary tract in 25% of cases. Microscopic renal anomalies were dominated by glomerulocystic kidney and renal dysplasia. Extra-renal manifestations such as pancreatic hypoplasia (75%) and genital anomalies (68%) were only detected at autopsy. In 40% of cases, there was heterozygous deletion of the whole gene. There were de novo mutations in 40%. CONCLUSION: This study underlines the importance of considering hepatocyte nuclear factor-1 β mutations in fetuses with congenital anomalies of the kidney and urinary tract, especially when associated with pancreatic hypoplasia. No correlation between phenotype and genotype was found, highlighting high intra-familial variability in cases with inherited mutations.
Authors: Rhian L Clissold; Jon Fulford; Michelle Hudson; Beverley M Shields; Timothy J McDonald; Sian Ellard; Andrew T Hattersley; Coralie Bingham Journal: Clin Kidney J Date: 2018-01-30
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