MUTATIONS IN THE SLC3A1 TRANSPORTER GENE IN CYSTINURIA

Cystinuria is an autosomal recessive disease characterized by the deve lopment of kidney stones. Guided by the identification of the SLC3A1 a mino acid-transport gene on chromosome 2, we recently established gene tic linkage of cystinuria to chromosome 2p in 17 families, without evi dence for locus heterogeneity. Other authors have independently identi fied missense mutations in SLC3A1 in cystinuria patients. In this repo rt we describe four additional cystinuria-associated mutations in this gene: a frameshift, a deletion, a transversion inducing a critical am ino acid change, and a nonsense mutation. The latter stop codon was fo und in ah of eight Ashkenazi Jewish carrier chromosomes examined, This report brings the number of disease-associated mutations in this gene to 10. We also assess the frequency of these mutations in our 17 cyst inuria families.