Genetic and Clinical Characteristics of Japanese Cystinuria with Exon and Exon-Intron Boundary Variants

Cystinuria is the most common genetic cause of urinary stones. Defect in SLC3A1 / SLC7A9 genes coding cystine transporter proteins rBAT/b ^0,+ AT will cause Cystinuria. The current work analyzed the clinical and genetics characteristics of Japanese Cystinuria patients. In total, 101 Cystinuria patients were studied. Clinical phenotypes were defined, and genetic analysis of SLC3A1 and SLC7A9 by next-generation sequence was performed. Excretion of urine cystine were determined by twenty-four hours urine analysis. The median age of presentation was 17 years old. In total, 51 different mutant variant alleles were identified (22 and 28 mutant variants in SLC3A1 and SLC7A9 , respectively), including 28 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 homozygote intron (exon-intron boundary) variant in SCL7A9 presented a severe phenotype with significant loss of mRNA expression. Inclusion of exon and exon-intron boundary variants reduced the number of cases that did not fit autosomal recessive inheritance from 14–9%. Predominance of p.pro482Leu (c.1445C > T) variant in SCL7A9 was a unique characteristic of Japanese Cystinuria. Current data may provide a rationale for the inclusion of exon-intron boundary variants in genomic classification.