title: Clinical manifestations in Israeli cystinuria patients and molecular assessment of carrier rates in Libyan Jewish controls.
abstract: BACKGROUND
  Cystinuria is an autosomal recessive disease that is manifested by the development of kidney stones. Mutations in SLC3A1 cause type I disease, while mutations in SLC7A9 are associated with non-type I disease. In Israel, cystinuria is especially common among Libyan Jews who suffer from non-type I disease.
  
  
  OBJECTIVE
  To compare clinical manifestations of patients with mutations in SLC3A1 to those with mutations in SLC7A9, and to assess the carrier rate among unaffected Libyan Jewish controls.
  
  
  METHODS
  Clinical manifestations were evaluated in patients with mutations in SLC3A1 and in patients with mutations in SLC7A9. Carrier rates for two SLC7A9 mutations were assessed in 287 unaffected Libyan Jewish controls.
  
  
  RESULTS
  Twelve patients with mutations in SLC3A1 were compared to 15 patients with mutations in SLC7A9. No differences were detected between the patients with mutations in SLC3A1 and those with mutations in SLC7A9 in relation to the age of disease onset, the estimated number of stones, the number of invasive procedures, the number of patients receiving drug therapy, or the patients' urinary pH. Eleven of the unaffected Libyan Jewish controls were found to be heterozygotes for the V170M mutation, establishing a carrier rate of 1:25. The 1584 + 3 del AAGT mutation was not found in any of the Libyan Jewish controls.
  
  
  CONCLUSIONS
  Mutations in SLC3A1 and SLC7A9 cystinuria patients result in indistinguishable disease manifestations. The high carrier rate among Libyan Jews is a result of a single missense mutation, V170M.
authors.affiliation: Danek Gartner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Roy
authors.initials: R
authors.lastname: Sidi
authors.forename: Etgar
authors.initials: E
authors.lastname: Levy-Nissenbaum
authors.forename: Y
authors.initials: Y
authors.lastname: Kreiss
authors.forename: Itzhak
authors.initials: I
authors.lastname: Kreiss
authors.forename: Elon
authors.initials: E
authors.lastname: Pras
mesh_terms: D017668:Age of Onset; D026923:Amino Acid Transport Systems, Basic; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D003555:Cystinuria / Q000150:complications / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D020732:Cytogenetic Analysis; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D006580:Genetic Carrier Screening; D005820:Genetic Testing; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007585:Jews / Q000235:genetics* / Q000706:statistics & numerical data; D008002:Libya / Q000453:epidemiology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D017720:Molecular Epidemiology; D020125:Mutation, Missense / Q000235:genetics*; D018579:Patient Selection; D010375:Pedigree; D015995:Prevalence; D017678:Sex Distribution; D014545:Urinary Calculi / Q000235:genetics
chemical_list: D026923:Amino Acid Transport Systems, Basic; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; C499489:SLC7A9 protein, human