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


CONCLUSIONS
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. © 2016 John Wiley & Sons, Ltd.
Service de Pathologie, Centre Hospitalier Princesse Grace, Avenue Pasteur, Monaco.|SOFFOET, Société Française de Fœtopathologie, Lyon, Rennes, France.
Hélène
H
Duval
Service d'Endocrinologie Moléculaire et Maladies Rares, Centre de Biologie et Pathologie Est, Bron, France.
Laurence
L
Michel-Calemard
SOFFOET, Société Française de Fœtopathologie, Lyon, Rennes, France.|Service de Génétique et d'Embryologie Médicales, Hôpital Armand Trousseau, APHP, UPMC, Paris, France.
Marie
M
Gonzales
SOFFOET, Société Française de Fœtopathologie, Lyon, Rennes, France.|Laboratoire d'Anatomie et de Cytologie Pathologiques, Hôpital Pontchaillou, Rennes, France.
Philippe
P
Loget
Service de Génétique Médicale, Institut de Biologie, CHU de Nantes, Nantes, France.
Claire
C
Beneteau
SOFFOET, Société Française de Fœtopathologie, Lyon, Rennes, France.|Centre de Pathologie Est, Hôpital Femme-Mère-Enfant, Groupement Hospitalier Est, Hospices Civils de Lyon, Lyon, France.
Annie
A
Buenerd
SOFFOET, Société Française de Fœtopathologie, Lyon, Rennes, France.|Service d'Anatomie Pathologique, CHU Hôtel Dieu, Nantes, France.
Madeleine
M
Joubert
Service d'Anatomie Pathologique, CHU Hôtel Dieu, Nantes, France.
Marielee
M
Denis-Musquer
SOFFOET, Société Française de Fœtopathologie, Lyon, Rennes, France.|Service d'Anatomie et Cytologie Pathologiques, CHU Saint-Etienne, Saint-Etienne, France.
Alix
A
Clemenson
SOFFOET, Société Française de Fœtopathologie, Lyon, Rennes, France.|Laboratoire d'Anatomie Pathologique-Neuropathologique, Hôpital de la Timone, Marseille, France.
Anne-Laure
AL
Chesnais
SOFFOET, Société Française de Fœtopathologie, Lyon, Rennes, France.|Service de Génétique, Centre Olympes de Gouges, Hôpital Bretonneau, CHRU de Tours, Tours, France.
Sophie
S
Blesson
Cabinet de Pathologie Léonard de Vinci Chambray Les Tours, Tours, France.
Isabelle
I
De Pinieux
SOFFOET, Société Française de Fœtopathologie, Lyon, Rennes, France.|Service de Biologie du Développement, Hôpital Robert Debré, APHP, Université Paris Diderot, Paris, France.
Anne-Lise
AL
Delezoide
Département de Génétique, Université Pierre et Marie Curie, Paris, France.
Gheorghe
G
Bonyhay
Département de Génétique, Université Pierre et Marie Curie, Paris, France.
Christine
C
Bellanné-Chantelot
Centre de Référence des Maladies Rénales Héréditaires de l'Enfant et de l'Adulte (MARHEA), AP-HP, Hôpital Necker, Paris, France.
Laurence
L
Heidet
Service de Pathologie, Centre Hospitalier Princesse Grace, Avenue Pasteur, Monaco.
Florence
F
Dupré
SOFFOET, Société Française de Fœtopathologie, Lyon, Rennes, France.|Centre de Pathologie Est, Hôpital Femme-Mère-Enfant, Groupement Hospitalier Est, Hospices Civils de Lyon, Lyon, France.|Université Claude Bernard Lyon 1, Lyon, France.
Sophie
S
Collardeau-Frachon
D001344:Autopsy; D000013:Congenital Abnormalities / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology; D005260:Female; D005838:Genotype; D051539:Hepatocyte Nuclear Factor 1-beta / Q000235:genetics*; D006801:Humans; D007668:Kidney / Q000002:abnormalities* / Q000000981:diagnostic imaging / Q000473:pathology; D008297:Male; D009154:Mutation; D010179:Pancreas / Q000002:abnormalities* / Q000000981:diagnostic imaging; D010182:Pancreatic Diseases / Q000151:congenital* / Q000000981:diagnostic imaging / Q000235:genetics; D010641:Phenotype; D011247:Pregnancy; D016216:Ultrasonography, Prenatal; D014564:Urogenital Abnormalities / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology
C496495:HNF1B protein, human; D051539:Hepatocyte Nuclear Factor 1-beta