Fetal anomalies associated with HNF1B mutations: report of 20 autopsy cases

Hélène Duval (1) , Laurence Michel-Calemard (2) , Marie Gonzales (3) , Philippe Loget (4) , Claire Beneteau (5) , Annie Buenerd (6) , Madeleine Joubert (7) , Marielee Denis-Musquer (8) , Alix Clemenson (9) , Anne-Laure Chesnais (10) , Sophie Blesson (11) , Isabelle de Pinieux (12) , Anne-Lise Delezoide (13) , Gheorghe Bonyhay (14) , Christine Bellanné-Chantelot (15) , Laurence Heidet (16) , Florence Dupré (1) , Sophie Collardeau-Frachon (17, 18)

1 CHPG - Centre Hospitalier Princesse Grace de Monaco
2 Centre de biologie et pathologie Est
3 Service de génétique et embryologie médicales [CHU Trousseau]
4 Service d'anatomie et cytologie pathologiques [Rennes] = Anatomy and Cytopathology [Rennes]
5 Service de génétique médicale - Unité de génétique clinique [Nantes]
6 Centre de Pathologie Est, Lyon
7 Service de Pathologie
8 Service d'Anatomie Pathologique
9 Service d’Anatomie et Cytologie Pathologiques
10 Laboratoire d'Anatomie Pathologique-Neuropathologique
11 Service de génétique [Tours]
12 Cabinet de Pathologie Léonard de Vinci
13 Service de Biologie du Développement
14 UPMC - Université Pierre et Marie Curie - Paris 6
15 Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière]
16 Service de néphrologie pédiatrique [CHU Necker]
17 UCBL - Université Claude Bernard Lyon 1
18 HCL - Hospices Civils de Lyon

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.

Domains: Life Sciences [q-bio]; Development Biology; Embryology and Organogenesis; Life Sciences [q-bio]; Human health and pathology; Gynecology and obstetrics; Life Sciences [q-bio]; Genetics; Human genetics

Hélène Duval, Laurence Michel-Calemard, Marie Gonzales, Philippe Loget, Claire Beneteau, et al.. Fetal anomalies associated with HNF1B mutations: report of 20 autopsy cases. Prenatal Diagnosis, 2016, 36, pp.744-751. ⟨10.1002/pd.4858⟩. ⟨hal-01494111⟩