title: Molecular and Clinical Investigation of Cystinuria in the Greek-Cypriot Population.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: 1 Department of Nephrology, Nicosia General Hospital , Nicosia, Cyprus .
authors.forename: Yiannis
authors.initials: Y
authors.lastname: Athanasiou
authors.affiliation: 2 Department of Biological Sciences and Molecular Medicine Research Center, University of Cyprus , Nicosia, Cyprus .
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Voskarides
authors.affiliation: 3 Laboratory of General Biology and Genetics, Medical School, Aristotle University of Thessaloniki , Greece .
authors.forename: Anthi
authors.initials: A
authors.lastname: Chatzikyriakidou
authors.affiliation: 2 Department of Biological Sciences and Molecular Medicine Research Center, University of Cyprus , Nicosia, Cyprus .
authors.forename: Anastasia
authors.initials: A
authors.lastname: Ignatiou
authors.affiliation: 2 Department of Biological Sciences and Molecular Medicine Research Center, University of Cyprus , Nicosia, Cyprus .
authors.forename: Panayiota
authors.initials: P
authors.lastname: Demosthenous
authors.affiliation: 4 Department of Pediatric/Pediatric Nephrology, Archbishop Makarios III Hospital , Nicosia, Cyprus .
authors.forename: Avraam
authors.initials: A
authors.lastname: Elia
authors.affiliation: 1 Department of Nephrology, Nicosia General Hospital , Nicosia, Cyprus .
authors.forename: Michalis
authors.initials: M
authors.lastname: Zavros
authors.affiliation: 5 Laboratory of Medical Genetics, Medical School, Ioannina University , Greece .
authors.forename: Ioannis
authors.initials: I
authors.lastname: Georgiou
authors.affiliation: 6 Department of Nephrology, Hippocrateon Hospital , Nicosia, Cyprus .
authors.forename: Alkis
authors.initials: A
authors.lastname: Pierides
authors.affiliation: 2 Department of Biological Sciences and Molecular Medicine Research Center, University of Cyprus , Nicosia, Cyprus .
authors.forename: Constantinos
authors.initials: C
authors.lastname: Deltas
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D026923:Amino Acid Transport Systems, Basic / Q000235:genetics*; D026921:Amino Acid Transport Systems, Neutral / Q000235:genetics*; D002648:Child; D003555:Cystinuria / Q000453:epidemiology / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006115:Greece / Q000453:epidemiology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000453:epidemiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction
chemical_list: D026923:Amino Acid Transport Systems, Basic; D026921:Amino Acid Transport Systems, Neutral; C489857:SLC3A1 protein, human; C499489:SLC7A9 protein, human