Identification of a novel genomic mutations through a next-generation sequence among Japanese Cystinuria patients

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Cystinuria is an autosomal recessive disease, caused by the two mutations in BAT1(SLC7A9)/rBAT(SLC3A1). Around 70% of Japanese Cystinuria patients possessed a characteristics mutation: P482L, which has not been found in European countries. Based on this unique genomic properties, some Japnese patients failed to fit into the genomic classification(two mutations in BAT1(B) or rBAT(A): one mutation in rBAT and BAT1(AB)). Here we studied the genomic profile of the fifty-one Japanese Cystinuria patients.


A next-generation sequence was performed among fifty-one patients who previously performed a direct sequence of SLC3A1/SCL7A9, including four patients without any mutation found previously and thirteen unclassifiable patients who possessed only a single mutation. Nextseq 500 was used for the sequencing. The result between previous direct sequence and a next-generation sequence were compared.


The median Cystine concentration was 217.4µM. Overall, 8 novel mutations were identified, includes 2 frameshift(fs) and 5 point mutations and one exon-intron boundary mutation. In SCL7A9, P482L homozygote and heterozygote were found in 16(31.4%) and 17(33.3%) of patients, respectively. Second common mutations were A354T, T69 stop and V340fs found in 2 patients. In SLC3A1, V183A was the most common mutations, found only in 2 patients. In terms of genotype classification, the number of type A, B and AB patients was 5, 34 and 2, respectively. Compare to direct sequence, 9 patients were reclassified into the novel genotype. However, overall 19.6% of patients still not fit into an autosomal recessive inheritance, with 2 patients possessed no mutation.


Among 51 patients, 8 novel mutations were identified and 9 patients were reclassified into a novel genotype. However, 20% of patients did not fit into autosomal recessive genotype. Current data may suggest the potential contribution of another factor in the pathogenesis of Cystinuria.

Funding: None