Heterogeneous mutations in the SLC3A1 and SLC7A9 genes in Chinese patients with cystinuria

Kidney Int. 2006 Jan;69(1):123-8. doi: 10.1038/sj.ki.5000003.

Abstract

Cystinuria is a recessively inherited aminoaciduria that leads to recurrent urolithiasis. It is caused by the defective transport of cystine and dibasic amino acids in the proximal renal tubules and intestinal epithelium. Two genes responsible for this, SLC3A1 and SLC7A9, are known. Patients with two SLC3A1 mutations are classified as type A cystinuria, whereas patients with two SLC7A9 mutations are classified as type B cystinuria. Few clinical and molecular data have been reported for Asian cystinuria patients. In this study, we determined the molecular basis of cystinuria in eight unrelated Chinese subjects. Coding exons and flanking introns of the SLC3A1 and SLC7A9 genes were directly sequenced after amplification by polymerase chain reaction. Five different SLC3A1 mutations were found. Two missense mutations, D210G and S547L, were novel. The other three SLC3A1 mutations (IVS6+2T>C, R181Q and R365W) have been described previously. In addition, four novel SLC7A9 mutations, C137R, c.730delG, IVS10+2_3delTG and IVS12+3insT, together with two previously reported mutations (A70V and G195R) were found. All patients except one carried compound heterozygous mutations. IVS12+3insT was detected in patients from two families. This is the first molecular genetic study on Chinese cystinuria patients. Three patients with type A cystinuria, two with type B cystinuria, and three carriers of type B cystinuria were identified. Our results suggest that the molecular basis of cystinuria is heterogeneous in our local population.

MeSH terms

  • Adult
  • Amino Acid Transport Systems, Basic / genetics*
  • Amino Acid Transport Systems, Neutral / genetics*
  • Child, Preschool
  • Cystine / metabolism
  • Cystinuria / genetics*
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Mutation*

Substances

  • Amino Acid Transport Systems, Basic
  • Amino Acid Transport Systems, Neutral
  • SLC3A1 protein, human
  • SLC7A9 protein, human
  • Cystine