title: Genotype-phenotype correlations in fetuses and neonates with autosomal recessive polycystic kidney disease.
abstract: The prognosis of autosomal recessive polycystic kidney disease is known to correlate with genotype. The presence of two truncating mutations in the PKHD1 gene encoding the fibrocystin protein is associated with neonatal death while patients who survive have at least one missense mutation. To determine relationships between genotype and renal and hepatic abnormalities we correlated the severity of renal and hepatic histological lesions to the type of PKHD1 mutations in 54 fetuses (medical pregnancy termination) and 20 neonates who died shortly after birth. Within this cohort, 55.5% of the mutations truncated fibrocystin. The severity of cortical collecting duct dilatations, cortical tubule and glomerular lesions, and renal cortical and hepatic portal fibrosis increased with gestational age. Severe genotypes, defined by two truncating mutations, were more frequent in patients of less than 30 weeks gestation compared to older fetuses and neonates. When adjusted to gestational age, the extension of collecting duct dilatation into the cortex and cortical tubule lesions, but not portal fibrosis, was more prevalent in patients with severe than in those with a non-severe genotype. Our results show the presence of two truncating mutations of the PKHD1 gene is associated with the most severe renal forms of prenatally detected autosomal recessive polycystic kidney disease. Their absence, however, does not guarantee survival to the neonatal period.
authors: Assistance Publique-Hôpitaux de Paris, Université Paris Diderot, Hôpital Robert Debré, Laboratoire de Biochimie Génétique, INSERM U722, Paris, France.
authors: Erick
authors: E
authors: Denamur
authors: Anne-Lise
authors: AL
authors: Delezoide
authors: Corinne
authors: C
authors: Alberti
authors: Agnès
authors: A
authors: Bourillon
authors: Marie-Claire
authors: MC
authors: Gubler
authors: Raymonde
authors: R
authors: Bouvier
authors: Olivier
authors: O
authors: Pascaud
authors: Jacques
authors: J
authors: Elion
authors: Bernard
authors: B
authors: Grandchamp
authors: Laurence
authors: L
authors: Michel-Calemard
authors: Pascale
authors: P
authors: Missy
authors: Isabelle
authors: I
authors: Zaccaria
authors: Hervé
authors: H
authors: Le Nagard
authors: Bénédicte
authors: B
authors: Gerard
authors: Chantal
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authors: Loirat
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authors: J
authors: Barbet
authors: A M
authors: AM
authors: Beaufrère
authors: C
authors: C
authors: Berchel
authors: B
authors: B
authors: Bessières
authors: S
authors: S
authors: Boudjemaa
authors: A
authors: A
authors: Buenerd
authors: D
authors: D
authors: Carles
authors: A
authors: A
authors: Clemenson
authors: P
authors: P
authors: Dechelotte
authors: L
authors: L
authors: Devisme
authors: F
authors: F
authors: Dijoud
authors: O
authors: O
authors: Espérandieu
authors: C
authors: C
authors: Fallet
authors: M
authors: M
authors: Gonzalès
authors: Y
authors: Y
authors: Hillion
authors: B
authors: B
authors: Jacob
authors: M
authors: M
authors: Joubert
authors: P
authors: P
authors: Kermanach
authors: A
authors: A
authors: Lallemand
authors: A
authors: A
authors: Laquerrière
authors: N
authors: N
authors: Laurent
authors: A
authors: A
authors: Liprandi
authors: L
authors: L
authors: Loeuillet
authors: P
authors: P
authors: Loget
authors: J
authors: J
authors: Martinovic
authors: F
authors: F
authors: Ménez
authors: F
authors: F
authors: Narcy
authors: J J
authors: JJ
authors: Roux
authors: C
authors: C
authors: Rouleau-Dubois
authors: M
authors: M
authors: Sinico
authors: J
authors: J
authors: Tantau
authors: A R
authors: AR
authors: Wann
mesh_terms: D005315:Fetal Diseases / Q000235:genetics* / Q000473:pathology*; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D009154:Mutation; D010641:Phenotype; D017044:Polycystic Kidney, Autosomal Recessive / Q000235:genetics* / Q000473:pathology*; D011956:Receptors, Cell Surface / Q000235:genetics*
chemical_list: C451750:PKHD1 protein, human; D011956:Receptors, Cell Surface