title: A novel gene encoding an SH3 domain protein is mutated in nephronophthisis type 1.
abstract: Juvenile nephronophthisis (NPH), an autosomal recessive cystic kidney disease, is the primary genetic cause of chronic renal failure in children. About two thirds of patients with NPH carry a large homozygous deletion at the gene locus NPH1 on 2q13. We here identify a novel gene. NPHP1, which extends over most of this common deletion. The 4.5-kb transcript encodes a protein with an SH3 domain, which is highly conserved throughout evolution. The 11-kb interval between the 3' end of NPHP1 and an inverted repeat containing the distal deletion breakpoint was found to contain the first exon of a second gene, MALL. In patients with a hemizygous deletion of the NPH1 region, additional point mutations were found in NPHP1 but not in MALL.
authors.affiliation: University Children's Hospital, Freiburg University, Germany. hildebra@sunt.uk1.uni-freiburg.de
authors.forename: F
authors.initials: F
authors.lastname: Hildebrandt
authors.forename: E
authors.initials: E
authors.lastname: Otto
authors.forename: C
authors.initials: C
authors.lastname: Rensing
authors.forename: H G
authors.initials: HG
authors.lastname: Nothwang
authors.forename: M
authors.initials: M
authors.lastname: Vollmer
authors.forename: J
authors.initials: J
authors.lastname: Adolphs
authors.forename: H
authors.initials: H
authors.lastname: Hanusch
authors.forename: M
authors.initials: M
authors.lastname: Brandis
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D003598:Cytoskeletal Proteins; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics / Q000302:isolation & purification; D005091:Exons; D015870:Gene Expression; D006801:Humans; D052177:Kidney Diseases, Cystic / Q000235:genetics*; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000235:genetics*; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D016324:Sequence Tagged Sites; D018909:src Homology Domains / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D018076:DNA, Complementary; D008565:Membrane Proteins; C108725:NPHP1 protein, human; D011506:Proteins