TY - JOUR
T1 - Molecular and Clinical Investigation of Cystinuria in the Greek-Cypriot Population
AU - Athanasiou, Yiannis
AU - Voskarides, Konstantinos
AU - Chatzikyriakidou, Anthi
AU - Ignatiou, Anastasia
AU - Demosthenous, Panayiota
AU - Elia, Avraam
AU - Zavros, Michalis
AU - Georgiou, Ioannis
AU - Pierides, Alkis
AU - Deltas, Constantinos
N1 - Publisher Copyright:
© Copyright 2015, Mary Ann Liebert, Inc.
PY - 2015/11
Y1 - 2015/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84947729866&partnerID=8YFLogxK
U2 - 10.1089/gtmb.2015.0144
DO - 10.1089/gtmb.2015.0144
M3 - Article
C2 - 26540609
AN - SCOPUS:84947729866
SN - 1945-0265
VL - 19
SP - 641
EP - 645
JO - Genetic Testing and Molecular Biomarkers
JF - Genetic Testing and Molecular Biomarkers
IS - 11
ER -