Linkage of the gene for cystinosis to markers on the short arm of chromosome 17. The Cystinosis Collaborative Research Group.

Nephropathic cystinosis (MIM 21980) is an autosomal recessive disorder due to defective transport of the amino acid cystine out of lysosomes. Cystine storage leads to acidosis, dehydration, rickets and growth retardation in the first year of life, followed by renal glomerular failure at approximately ten years of age. Renal transplantation is highly successful, but cystine continues to accumulate in other tissues, resulting in complications such as corneal ulcerations and retinal blindness, a distal vacuolar myopathy, delayed puberty, swallowing difficulties, pancreatic deficiency and central nervous system involvement. Treatment with the cysteine-depleting agent, cysteamine (Cystagon), or phosphocysteamine, has proven successful in retarding glomerular deterioration and enhancing growth. Although cystinosis represents the prototypic disorder of lysosomal membrane transport, neither the cystinosis gene nor the lysosomal cystine carrier has been isolated. We now report linkage of the cystinosis gene to markers on the short arm of chromosome 17 (Zmax = 10.89, theta = 0.03) for marker D17S1584. Multipoint analysis and haplotypes in recombinant families suggest that the gene is located between markers D17S1583 and D17S796.