title: Clinical and histological presentation of 3 siblings with mutations in the NPHP4 gene.
abstract: Nephronophthisis (NPH) is an autosomal recessive kidney disease characterized by tubular basement membrane disruption, interstitial infiltration, and tubular cysts. NPH leads to end-stage renal failure in the first 2 decades of life. Four genes responsible for different types of NPH have been identified: NPHP1, NPHP2, NPHP3, and NPHP4. The NPHP1 gene encodes nephrocystin; NPHP2, inversin; NPHP3, nephrocystin-3; and NPHP4, nephrocystin-4. We report 3 siblings from a consanguineous family with NPH who were previously described as carrying a homozygous mutation in the NPHP4 gene. Renal imaging showed cysts in the children. The histological picture of NPHP4 showed the same characteristic features as those known for NPHP1 and NPHP3. Progression to end-stage renal disease occurred between the ages of 17 and 22 years. None of the renal transplants showed recurrence of the disease. Retinitis pigmentosa was absent in all affected family members.
authors.affiliation: Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Julia
authors.initials: J
authors.lastname: Hoefele
authors.forename: Edgar
authors.initials: E
authors.lastname: Otto
authors.forename: Helmut
authors.initials: H
authors.lastname: Felten
authors.forename: Karlwilhelm
authors.initials: K
authors.lastname: Kühn
authors.forename: Thorsten A
authors.initials: TA
authors.lastname: Bley
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Zäuner
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Hildebrandt
authors.forename: Hartmut P H
authors.initials: HP
authors.lastname: Neumann
mesh_terms: D000006:Abdomen, Acute / Q000209:etiology; D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D001827:Body Height; D002352:Carrier Proteins / Q000235:genetics*; D003598:Cytoskeletal Proteins; D005260:Female; D006801:Humans; D052177:Kidney Diseases, Cystic / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D007676:Kidney Failure, Chronic / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D016030:Kidney Transplantation; D008297:Male; D008565:Membrane Proteins; D009154:Mutation; D010375:Pedigree; D011506:Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; C108725:NPHP1 protein, human; C491578:NPHP4 protein, human; D011506:Proteins