title: A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis.
abstract: Nephropathic cystinosis, an autosomal recessive disorder resulting from defective lysosomal transport of cystine, is the most common inherited cause of renal Fanconi syndrome. The cystinosis gene has been mapped to chromosome 17p13. We found that the locus D17S829 was homozygously deleted in 23 out of 70 patients, and identified a novel gene, CTNS, which mapped to the deletion interval. CTNS encodes an integral membrane protein, cystinosin, with features of a lysosomal membrane protein. Eleven different mutations, all predicted to cause loss of function of the protein, were found to segregate with the disorder.
authors.affiliation: Division of Medical and Molecular Genetics, United Medical and Dental Schools, Guy's Hospital, London, UK. m.town@umds.ac.uk
authors.forename: M
authors.initials: M
authors.lastname: Town
authors.forename: G
authors.initials: G
authors.lastname: Jean
authors.forename: S
authors.initials: S
authors.lastname: Cherqui
authors.forename: M
authors.initials: M
authors.lastname: Attard
authors.forename: L
authors.initials: L
authors.lastname: Forestier
authors.forename: S A
authors.initials: SA
authors.lastname: Whitmore
authors.forename: D F
authors.initials: DF
authors.lastname: Callen
authors.forename: O
authors.initials: O
authors.lastname: Gribouval
authors.forename: M
authors.initials: M
authors.lastname: Broyer
authors.forename: G P
authors.initials: GP
authors.lastname: Bates
authors.forename: W
authors.initials: W
authors.lastname: van't Hoff
authors.forename: C
authors.initials: C
authors.lastname: Antignac
mesh_terms: D000595:Amino Acid Sequence; D026921:Amino Acid Transport Systems, Neutral; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D003001:Cloning, Molecular; D003360:Cosmids / Q000235:genetics; D003554:Cystinosis / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005192:Family Health; D005260:Female; D017353:Gene Deletion; D015870:Gene Expression / Q000235:genetics; D005796:Genes / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics; D006023:Glycoproteins; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics / Q000502:physiology; D018807:Polymorphism, Single-Stranded Conformational; D017386:Sequence Homology, Amino Acid
chemical_list: D026921:Amino Acid Transport Systems, Neutral; C111445:CTNS protein, human; D005819:Genetic Markers; D006023:Glycoproteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins