title: Comprehensive PKD1 and PKD2 Mutation Analysis in Prenatal Autosomal Dominant Polycystic Kidney Disease.
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.
authors.affiliation: Laboratory of Molecular Genetics and Histocompatibility, University Hospital of Brest, Institut National de la Santé et de la Recherche Médicale, U1078, Brest, France;
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Audrézet
authors.affiliation: Assistance Publique des Hôpitaux de Paris, Centre de référence des Maladies Rénales Héréditaires de l'Enfant et de l'Adulte (MARHEA), Department of Pediatric Nephrology, University Hospital Necker-Enfants Malades Paris, France;
authors.forename: Christine
authors.initials: C
authors.lastname: Corbiere
authors.affiliation: Assistance Publique des Hôpitaux de Paris, Centre de référence des Maladies Rénales Héréditaires de l'Enfant et de l'Adulte (MARHEA), Department of Pediatric Nephrology, University Hospital Necker-Enfants Malades Paris, France;
authors.forename: Said
authors.initials: S
authors.lastname: Lebbah
authors.affiliation: Assistance Publique des Hôpitaux de Paris, Centre de référence des Maladies Rénales Héréditaires de l'Enfant et de l'Adulte (MARHEA), Department of Pediatric Nephrology, University Hospital Necker-Enfants Malades Paris, France;
authors.forename: Vincent
authors.initials: V
authors.lastname: Morinière
authors.affiliation: Department of Medical Pediatrics, Pediatric Nephrology and Hemodialysis Unit, University Hospital Charles Nicolle, Rouen, France;
authors.forename: Françoise
authors.initials: F
authors.lastname: Broux
authors.affiliation: Department of Medical Pediatrics, Pediatric Nephrology and Hemodialysis Unit, University Hospital Charles Nicolle, Rouen, France;
authors.forename: Ferielle
authors.initials: F
authors.lastname: Louillet
authors.affiliation: Department of Pediatrics 1, University Hospital of Strasbourg Strasbourg, France;
authors.forename: Michel
authors.initials: M
authors.lastname: Fischbach
authors.affiliation: Department of Pediatrics 1, University Hospital of Strasbourg Strasbourg, France;
authors.forename: Ariane
authors.initials: A
authors.lastname: Zaloszyc
authors.affiliation: Department of Pediatric Nephrology and Hemodialysis, Clocheville Hospital, University Hospital of Tours, Tours, France;
authors.forename: Sylvie
authors.initials: S
authors.lastname: Cloarec
authors.affiliation: Department of Pediatric Nephrology and Hemodialysis, Clocheville Hospital, University Hospital of Tours, Tours, France;
authors.forename: Elodie
authors.initials: E
authors.lastname: Merieau
authors.affiliation: Assistance publique des Hôpitaux de Paris, Department of Pediatric Nephrology, University Hospital Robert Debré, Paris, France;
authors.forename: Véronique
authors.initials: V
authors.lastname: Baudouin
authors.affiliation: Assistance publique des Hôpitaux de Paris, Department of Pediatric Nephrology, University Hospital Robert Debré, Paris, France;
authors.forename: Georges
authors.initials: G
authors.lastname: Deschênes
authors.affiliation: Pediatric Department, Nantes University Hospital, Nantes, France;
authors.forename: Gwenaelle
authors.initials: G
authors.lastname: Roussey
authors.affiliation: Laboratory of Molecular Genetics and Histocompatibility, University Hospital of Brest, Institut National de la Santé et de la Recherche Médicale, U1078, Brest, France;
authors.forename: Sandrine
authors.initials: S
authors.lastname: Maestri
authors.affiliation: Assistance Publique des Hôpitaux de Paris, Centre de référence des Maladies Rénales Héréditaires de l'Enfant et de l'Adulte (MARHEA), Department of Pediatric Nephrology, University Hospital Necker-Enfants Malades Paris, France;
authors.forename: Chiara
authors.initials: C
authors.lastname: Visconti
authors.affiliation: Assistance Publique des Hôpitaux de Paris, Centre de référence des Maladies Rénales Héréditaires de l'Enfant et de l'Adulte (MARHEA), Department of Pediatric Nephrology, University Hospital Necker-Enfants Malades Paris, France; Institut National de la Santé et de la Recherche Médicale U1163, Laboratory of Hereditary Kidney Diseases, Université Paris Descartes Sorbonne Paris Cité, Paris, France;
authors.forename: Olivia
authors.initials: O
authors.lastname: Boyer
authors.affiliation: Department of Medical Genetics, Hospices Civils de Lyon, De la Croix Rousse Hospital Lyon, France;
authors.forename: Carine
authors.initials: C
authors.lastname: Abel
authors.affiliation: Pediatric Nephrology Unit Jeanne de Flandre Hospital, Regional University Hospital of Lille, Lille, France;
authors.forename: Annie
authors.initials: A
authors.lastname: Lahoche
authors.affiliation: Medical Genetics Unit, University Hospital St Pierre La Réunion, La Réunion, France;
authors.forename: Hanitra
authors.initials: H
authors.lastname: Randrianaivo
authors.affiliation: Department of Pediatrics and Pediatric Nephrology University Hospital Estaing, Clermont Ferrand, France;
authors.forename: Lucie
authors.initials: L
authors.lastname: Bessenay
authors.affiliation: Department of Pediatric Nephrology, University Hospitals Leuven, Leuven, Belgium;
authors.forename: Djalila
authors.initials: D
authors.lastname: Mekahli
authors.affiliation: Department of Congenital and Inherited Diseases Charles Nicolle Hospital, Tunis, Tunisia;
authors.forename: Ines
authors.initials: I
authors.lastname: Ouertani
authors.affiliation: Department of Pediatric Nephrology, Children Hospital Toulouse, France; and.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Decramer
authors.affiliation: Pediatric Department, University Hospital, Rennes, France.
authors.forename: Amélie
authors.initials: A
authors.lastname: Ryckenwaert
authors.affiliation: Laboratory of Molecular Genetics and Histocompatibility, University Hospital of Brest, Institut National de la Santé et de la Recherche Médicale, U1078, Brest, France;
authors.forename: Emilie
authors.initials: E
authors.lastname: Cornec-Le Gall
authors.affiliation: Assistance Publique des Hôpitaux de Paris, Centre de référence des Maladies Rénales Héréditaires de l'Enfant et de l'Adulte (MARHEA), Department of Pediatric Nephrology, University Hospital Necker-Enfants Malades Paris, France; Institut National de la Santé et de la Recherche Médicale U1163, Laboratory of Hereditary Kidney Diseases, Université Paris Descartes Sorbonne Paris Cité, Paris, France;
authors.forename: Rémi
authors.initials: R
authors.lastname: Salomon
authors.affiliation: Laboratory of Molecular Genetics and Histocompatibility, University Hospital of Brest, Institut National de la Santé et de la Recherche Médicale, U1078, Brest, France;
authors.forename: Claude
authors.initials: C
authors.lastname: Ferec
authors.affiliation: Assistance Publique des Hôpitaux de Paris, Centre de référence des Maladies Rénales Héréditaires de l'Enfant et de l'Adulte (MARHEA), Department of Pediatric Nephrology, University Hospital Necker-Enfants Malades Paris, France; laurence.heidet@nck.aphp.fr.
authors.forename: Laurence
authors.initials: L
authors.lastname: Heidet
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005220:Fathers; D005260:Female; D051539:Hepatocyte Nuclear Factor 1-beta / Q000235:genetics; D006801:Humans; D007223:Infant; D007676:Kidney Failure, Chronic / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009035:Mothers; D009154:Mutation; D010375:Pedigree; D016891:Polycystic Kidney, Autosomal Dominant / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics; D012189:Retrospective Studies; D050396:TRPP Cation Channels / Q000235:genetics*; D016216:Ultrasonography, Prenatal; D055815:Young Adult
chemical_list: D051539:Hepatocyte Nuclear Factor 1-beta; D011956:Receptors, Cell Surface; D050396:TRPP Cation Channels; C496495:HNF1B protein, human; C451750:PKHD1 protein, human
keywords: cystic kidney; human genetics; pediatrics; polycystic kidney disease