A NOVEL GENE ENCODING AN INTEGRAL MEMBRANE-PROTEIN IS MUTATED IN NEPHROPATHIC CYSTINOSIS

Nephropathic cystinosis, an autosomal recessive disorder resulting fro m defective lysosomal transport of cystine, is the most common inherit ed cause of renal Fanconi syndrome. The cystinosis gene has been mappe d to chromosome 17p13. We found that the locus D17S829 was homozygousl y deleted in 23 out of 70 patients, and identified a novel gene, CTNS, which mapped to the deletion interval. CTNS encodes an integral membr ane 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.