title: Mutations of NPHP2 and NPHP3 in infantile nephronophthisis.
abstract: Nephronophthisis is an autosomal recessive chronic tubulointerstitial disease that progresses to end-stage renal disease (ESRD) in about 10% of cases during infancy. Mutations in the INVS (NPHP2) gene were found in a few patients with infantile nephronophthisis. Mutations of NPHP3, known to be associated with adolescent nephronophthisis, were found in two patients with early-onset ESRD. Here we screened 43 families with infantile nephronophthisis (ESRD less than 5 years of age) for NPHP2 and NPHP3 mutations and determined genotype-phenotype correlations. In this cohort there were 16 families with NPHP2 mutations and NPHP3 mutations in seven. Three patients carried only one heterozygous mutation in NPHP3. ESRD arose during the first 2 years of life in 16 of 18 patients with mutations in NPHP2, but in only two patients with mutations in NPHP3. Renal morphology, characterized by hyper-echogenic kidneys on ultrasound and tubular lesions with interstitial fibrosis on histology, was similar in the two patient groups. The kidney sizes were highly diverse and ultrasound-visualized cysts were present in a minority of cases. Extra-renal anomalies were found in 80% of the entire cohort including hepatic involvement (50%), cardiac valve or septal defects (20%) and recurrent bronchial infections (18%). We show that NPHP3 mutations in both infantile and adolescent nephronophthisis point to a common pathophysiological mechanism despite their different clinical presentations.
authors.affiliation: Inserm, Paris, France.
authors.forename: Kálmán
authors.initials: K
authors.lastname: Tory
authors.forename: Caroline
authors.initials: C
authors.lastname: Rousset-Rouvière
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Gubler
authors.forename: Vincent
authors.initials: V
authors.lastname: Morinière
authors.forename: Audrey
authors.initials: A
authors.lastname: Pawtowski
authors.forename: Céline
authors.initials: C
authors.lastname: Becker
authors.forename: Claude
authors.initials: C
authors.lastname: Guyot
authors.forename: Sophie
authors.initials: S
authors.lastname: Gié
authors.forename: Yaacov
authors.initials: Y
authors.lastname: Frishberg
authors.forename: Hubert
authors.initials: H
authors.lastname: Nivet
authors.forename: Georges
authors.initials: G
authors.lastname: Deschênes
authors.forename: Pierre
authors.initials: P
authors.lastname: Cochat
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Gagnadoux
authors.forename: Sophie
authors.initials: S
authors.lastname: Saunier
authors.forename: Corinne
authors.initials: C
authors.lastname: Antignac
authors.forename: Rémi
authors.initials: R
authors.lastname: Salomon
mesh_terms: D000293:Adolescent; D002675:Child, Preschool; D018450:Disease Progression; D005192:Family Health; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D007674:Kidney Diseases / Q000235:genetics*; D007676:Kidney Failure, Chronic / Q000235:genetics; D016547:Kinesins / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C114503:INVS protein, human; D014157:Transcription Factors; C528697:nephrocystin-3, human; D016547:Kinesins