Cystinuria is an autosomal recessive disease in which there is excessive excretion of cystine in the urine, with precipitation of urinary cystine stones. Patients with this disorder may have renal colic, urinary tract obstruction, secondary urinary tract infections, and, if untreated, renal insufficiency. The chromosomal location of the cystinuria gene and the biochemical basis of cystinuria are unknown. The purpose of this project is to identify the chromosomal location of the cystinuria gene. During the first year of this project we have obtained peripheral blood samples from 9 cystinuria families (52 individuals, 22 affected). In most cases Epstein-Barr virus-transformed B cell lines were established. Genomic DNA was isolated from cell lines and/or freshly isolated lymphocytes. We began our genetic studies by testing for linkage to chromosome 16, since we had observed a Libyan Jewish family in which cystinuria co- segregated with familial Mediterranean fever (encoded on chromosome (16p). Using the larger panel of families and a group of highly informative microsatellite markers, we were unable to confirm linkage of the cystinuria gene to the short arm of chromosome 16. We have subsequently begun a systematic search of the genome to identify the chromosomal location of the cystinuria gene. After having examined approximately 40 additional markers, we do not yet have conclusive evidence placing the cystinuria gene on a specific chromosome. During the next year we plan to continue this search, examining markers spaced at 20 Cm intervals throughout the genome.
