title: PAX2 mutations in fetal renal hypodysplasia.
abstract: Papillorenal syndrome also known as renal-coloboma syndrome (OMIM 120330) is an autosomal dominant condition comprising optic nerve anomaly and renal oligomeganephronic hypoplasia. This reduced number of nephron generations with compensatory glomerular hypertrophy leads towards chronic insufficiency with renal failure. We report on two fetuses with PAX2 mutations presenting at 24 and 18 weeks' gestation, respectively, born into two different sibships. In our first patient, termination of pregnancy was elected for anhydramnios and suspicion of renal agenesis in the healthy couple with an unremarkable previous clinical history. This fetus had bilateral asymmetric kidney anomalies including a small multicystic left kidney, and an extremely hypoplastic right kidney. Histology showed dysplastic lesions in the left kidney, contrasting with rather normal organization in the hypoplastic right kidney. Ocular examination disclosed bilateral optic nerve coloboma. The association of these anomalies, highly suggestive of the papillorenal syndrome, led us to perform the molecular study of the PAX2 gene. Direct sequencing of the PAX2 coding sequence identified a de novo single G deletion of nucleotide 935 in exon 3 of the PAX2 resulting in a frameshift mutation (c.392delG, p.Ser131Thrfs*28). In the second family, the presence of a maternally inherited PAX2 mutation led to a decision for termination of pregnancy. The 18-week gestation fetus presented the papillorenal syndrome including hypoplastic kidneys and optic nerve coloboma. In order to address the PAX2 involvement in isolated renal "disease," 18 fetuses fulfilling criteria were screened: 10/18 had uni- or bilateral agenesis, 6/18 had bilateral multicystic dysplasia with enlarged kidneys, and 2/18 presented bilateral severe hypodysplasia confirmed on fetopathological examination. To the best of our knowledge, our first patient represents an unreported fetal diagnosis of papillorenal syndrome, and another example of the impact of oriented fetopathological examination in genetic counseling of the parents.
authors.affiliation: AP-HP, Unit of Embryo-Fetal Pathology, Department of Histo-Embryology and Cytogenetics, Necker Hospital, Paris, France. jelena.martinovic@nck.aphp.fr
authors.forename: Jelena
authors.initials: J
authors.lastname: Martinovic-Bouriel
authors.forename: Alexandra
authors.initials: A
authors.lastname: Benachi
authors.forename: Maryse
authors.initials: M
authors.lastname: Bonnière
authors.forename: Nora
authors.initials: N
authors.lastname: Brahimi
authors.forename: Chantal
authors.initials: C
authors.lastname: Esculpavit
authors.forename: Nicole
authors.initials: N
authors.lastname: Morichon
authors.forename: Michel
authors.initials: M
authors.lastname: Vekemans
authors.forename: Corinne
authors.initials: C
authors.lastname: Antignac
authors.forename: Rémi
authors.initials: R
authors.lastname: Salomon
authors.forename: Féréchté
authors.initials: F
authors.lastname: Encha-Razavi
authors.forename: Tania
authors.initials: T
authors.lastname: Attié-Bitach
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Gubler
mesh_terms: D000293:Adolescent; D000328:Adult; D004252:DNA Mutational Analysis; D005123:Eye / Q000473:pathology; D005124:Eye Abnormalities / Q000235:genetics / Q000473:pathology; D005260:Female; D005333:Fetus / Q000002:abnormalities*; D006801:Humans; D007668:Kidney / Q000002:abnormalities* / Q000473:pathology; D007674:Kidney Diseases / Q000235:genetics* / Q000473:pathology*; D009154:Mutation / Q000235:genetics*; D051762:PAX2 Transcription Factor / Q000235:genetics*; D011247:Pregnancy
chemical_list: D051762:PAX2 Transcription Factor; C497318:PAX2 protein, human