Molecular and Clinical Investigation of Cystinuria in the Greek-Cypriot Population

Genet Test Mol Biomarkers. 2015 Nov;19(11):641-5. doi: 10.1089/gtmb.2015.0144. Epub 2015 Nov 5.

Abstract

Background and aims: Cystinuria represents 3% of nephrolithiasis in humans. Two genes have been identified as the main genetic causes of cystinuria, SLC3A1 and SLC7A9, with an autosomal recessive mode of inheritance. In the present study, we studied for the first time, genetically and clinically, all the cystinuric families identified so far in the Greek-Cypriot population.

Methods: Discovery of mutations was performed through polymerase chain reaction (PCR)-single analysis and DNA resequencing. New families were investigated through PCR-RFLPs. Clinical data were collected through the hospital patients' records and analytical follow-up of the families.

Results and discussion: We found a total of five mutations in 28 Greek-Cypriot cystinuric patients belonging in 12 families. The most frequent mutation among the 28 Greek-Cypriot patients is the SLC3A1-p.T216M, which is also the second most frequent mutation in Europe, representing a genetic founder effect. Sixteen of the 28 patients are homozygous for this mutation. Even though a consanguinity loop was obvious in only one family, other patients were from families in small villages where endogamy was practiced for many centuries. Timely clinical and genetic diagnosis, accompanied by early treatment, is significant for the good health of most of our patients. Only ∼14% of them developed chronic renal failure, and only one reached end-stage renal disease (ESRD).

Conclusion: Five SLC3A1 and SLC7A9 mutations appear to be responsible for the genetic basis of cystinuria in the Greek-Cypriot patients; having such a limited number of causative mutations will simplify diagnostics for this population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Amino Acid Transport Systems, Basic / genetics*
  • Amino Acid Transport Systems, Neutral / genetics*
  • Child
  • Cystinuria / epidemiology
  • Cystinuria / genetics*
  • DNA Mutational Analysis
  • Female
  • Greece / epidemiology
  • Humans
  • Kidney Failure, Chronic / epidemiology
  • Kidney Failure, Chronic / genetics
  • Male
  • Middle Aged
  • Mutation
  • Pedigree
  • Polymerase Chain Reaction

Substances

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