A novel gene encoding an SH3 domain protein is mutated in nephronophthisis type 1.
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.
Hildebrandt
F
F
University Children's Hospital, Freiburg University, Germany. hildebra@sunt.uk1.uni-freiburg.de
Otto
E
E
Rensing
C
C
Nothwang
H G
HG
Vollmer
M
M
Adolphs
J
J
Hanusch
H
H
Brandis
M
M
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*
D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D018076:DNA, Complementary; D008565:Membrane Proteins; C108725:NPHP1 protein, human; D011506:Proteins