Advances in genetic aspects of cystinuria

Cystinuria has been clinically classified into three subtypes (I, II, and III) by Rosenberg and associates. In 1994, the SLC3A1 (rBAT) genes which is one of the genes responsible for cystinuria, was located on chromosome 2(2p21). However, it was demonstrated that rBAT is responsible only for Type I cystinuria. At present, 43 mutations, including 5 discovered in our laboratory, have been reported in the rBAT gene of patients with cystinuria. Recent studies suggest that the rBAT-encoded protein was not a transporter itself; rather, the protein represented a specific "guidance molecule" for a selected amino acid transporter. In 1999, the SLC7A9 (BAT1) gene was located on chromosome 19(19q13) by us and by a European group. It seemed that the BAT1 gene is responsible for non-Type I cystinuria and that its protein was a subunit linked to the rBAT protein via a disulfide bond. Mutational, structural, and functional analyses of the gene have been performed by several groups, including our laboratory. It is expected that the roles of these genes in cystinuria will be clarified further, and genetic diagnosis and therapy of patients with cystinuria may be facilitated in the future.