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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adaptor Proteins, Signal Transducing
-
Amino Acid Sequence
-
Base Sequence
-
Child
-
Cytoskeletal Proteins
-
DNA Mutational Analysis
-
DNA Primers / genetics
-
DNA, Complementary / genetics
-
DNA, Complementary / isolation & purification
-
Exons
-
Gene Expression
-
Humans
-
Kidney Diseases, Cystic / genetics*
-
Membrane Proteins
-
Molecular Sequence Data
-
Mutation*
-
Polymerase Chain Reaction
-
Polymorphism, Single-Stranded Conformational
-
Proteins / genetics*
-
Sequence Deletion
-
Sequence Homology, Amino Acid
-
Sequence Tagged Sites
-
src Homology Domains / genetics*
Substances
-
Adaptor Proteins, Signal Transducing
-
Cytoskeletal Proteins
-
DNA Primers
-
DNA, Complementary
-
Membrane Proteins
-
NPHP1 protein, human
-
Proteins