Identification of five novel SLC3A1 (rBAT) gene mutations in Japanese cystinuria

Background. Cystinuria is an inheritable amino aciduria and has been classified into three subtypes: I, II, and III. One of the genes responsible for cystinuria has recently been identified as SLC3Al or rBAT, but only type I cystinuria seems to be caused by genetic alterations in rBAT. To our knowledge, thus far 38 mutations in rBAT gene have been described. In this study, we investigated rBAT mutations in Japanese patients and compared the results with the previously reported mutations in other races. Methods. We investigated 36 Japanese cystinuria patients by mutational analysis of rBAT gene. To identify newly mutated alleles, genomic DNA was analyzed by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). When an abnormal migration was observed on SSCP, a nucleotide sequence determination was performed. Results. Five novel mutations were identified in five patients, three with missense mutations (L346P, I445T, C673R), one with a 1 bp deletion (1820delT), and one with a 2 bp insertion (1898insTA), and we detected three previously reported polymorphisms. Three of the mutations were homozygous, in whom parents had intermarried, and two were heterozygous for each mutations. Analysis of rBAT in family of the 1898insTA patient revealed that the patient had inherited the mutated allele from his parents. Conclusion. Five novel mutations in the rBAT gene have been identified in Japanese patients with cystinuria. A racial difference was not apparent in the position and frequency of the mutations.