Analysis of the genes SLC7A9 and SLC3A1 in unclassified cystinurics: mutation detection rates and association between variants in SLC7A9 and the disease

Clin Nephrol. 2002 May;57(5):342-8. doi: 10.5414/cnp57342.


Cystinuria is a common inherited disorder of defective renal reabsorption of cystine and dibasic amino acids. Recently, 2 responsible genes have been identified: mutations in the SLC3AI gene encoding the glycoprotein rBAT cause cystinuria type I, while variants in the SLC7A9 gene have been demonstrated in non-type I cystinuria; its gene product b(0)+AT is the light chain of the renal cystine transport system rBAT/b(0),+-AT. To estimate the role of both genes in the etiology of cystinuria, we searched for sequence alterations in SLC7A9 and SLC3AI: 30 unclassified cystinurics were investigated. In 50% of patients (15/30), point mutations in SLC3A1 were detected. Screening of the SLC7A9 gene revealed 10 mutations in 8 patients corresponding to a frequency of 27%. In addition to previously published mutations in the SLC7A9 gene, we detected 2 new mutations (F 140S, c747delG). An overall detection rate of 73% (22/30) in unclassified patients is delineated for mutations in both genes. In 33% (10/30), 2 mutations were detected, in 40% (12/30) 1 mutation. Furthermore, 5 new polymorphic sites were identified in SLC7A9. While the base pair variation in intron 9 is homogeneously distributed in patients and control individuals, the allelic and genotypic distributions of the polymorphisms in 3 exons of SLC7A9--exons 2, 5 and 6--and intron 3 differ significantly between both groups. Our results suggest that some haplotypes defined through the exons 2, 5 and 6 and intron 3 might be markers of a functional variant in the SLC7A9 gene. Evidently, since the mutation detection rates in the 2 so far known cystinuria genes never reach 100%, further genes and modulating factors should influence the phenotype in a subset of patients. However, the presented data show that testing for mutations in the 2 currently known cystinuria genes is already a meaningful approach to the molecular diagnostics of the disease.

MeSH terms

  • Amino Acid Transport Systems, Basic*
  • Carrier Proteins / genetics*
  • Cystinuria / classification
  • Cystinuria / diagnosis
  • Cystinuria / genetics*
  • Exons / genetics
  • Gene Frequency
  • Genotype
  • Heterozygote
  • Humans
  • Introns / genetics
  • Membrane Glycoproteins / genetics*
  • Point Mutation*
  • Polymorphism, Genetic


  • Amino Acid Transport Systems, Basic
  • Carrier Proteins
  • Membrane Glycoproteins
  • SLC7A9 protein, human