Nature Genetics
18, 319 - 324 (1998)
doi:10.1038/ng0498-319
A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosisMargaret Town1, 6, Geneviève Jean2, Stèphanie Cherqui2, Marlene Attard1, Lionel Forestier2, Scott A. Whitmore3, David F. Callen3, Olivier Gribouval2, Michel Broyer4, Gillian P. Bates1, William van't Hoff5
& Corinne Antignac2, 7
1Division of Medical and Molecular Genetics, United Medical and Dental Schools, 7th. Floor, Guy's Tower, Guy's Hospital, London SE1 9RT, UK.
2INSERM U423, Tour Lavoisier, Universite Rene Descartes, 149 rue de Sevres, 7'5015 Paris, France.
3Department of Cytogenetics and Molecular Genetics, Women's and Children's Hospital, 72 King William Road, North Adelaide, Australia.
4Service de Néphrologie Pédiatrique, Hôpital Necker-Enfants Malades, Université René Descartes, 149 rue de Sèvres, 7'5015 Paris, France.
5Nephrourology Unit, Institute of Child Health, University College London Medical School, 30 Guilford Street, London WC1N1EH, UK.
6(e-mail: m.town@umds.ac.uk)
7(e-mail: antignac@necker.fr) 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.
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