Genetic and clinical characteristics of Japanese cystinuria with exon and exon–intron boundary variants

Cystinuria is the most common genetic cause of urinary stones. Defects in SLC3A1/SLC7A9 genes coding cystine transporter proteins rBAT/b^0,+AT will cause Cystinuria. The current work analyzed the clinical and genetic characteristics of Japanese Cystinuria patients. In total, 101 Cystinuria patients were studied. Clinical phenotypes were defined, and genetic analysis of SLC3A1 and SLC7A9 was performed by next-generation sequencing. Excretion of cystine was determined by 24 h urine analysis. The median age of presentation was 17 years. In total, 51 different mutant variant alleles were identified (22 and 29 mutant variants in SLC3A1 and SLC7A9, respectively), including 25 novel variants. The p.(Pro482Leu) (c.1445C > T) variant in SCL7A9 was predominantly found in 73 patients. Variants in exon–intron boundaries were identified in 6 cases. The patient with a homozygote intron (exon–intron boundary) variant in SCL7A9 presented a severe phenotype with a significant loss of mRNA expression. Including exon and exon–intron boundary variants reduced the number of cases that did not fit autosomal recessive inheritance from 14 to 9%. Current data revealed a specific genotype of Japanese cystinuria through the analysis of exon and exon–intron boundaries.