Athanasiou Yiannis, Voskarides Konstantinos, Chatzikyriakidou Anthi, Ignatiou Anastasia, Demosthenous Panayiota, Elia Avraam, Zavros Michalis, Georgiou Ioannis, Pierides Alkis, Deltas Constantinos
1 Department of Nephrology, Nicosia General Hospital , Nicosia, Cyprus .
2 Department of Biological Sciences and Molecular Medicine Research Center, University of Cyprus , Nicosia, Cyprus .
Genet Test Mol Biomarkers. 2015 Nov;19(11):641-5. doi: 10.1089/gtmb.2015.0144. Epub 2015 Nov 5.
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.
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.
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).
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.
胱氨酸尿症占人类肾结石病例的3%。已确定两个基因SLC3A1和SLC7A9是胱氨酸尿症的主要遗传病因，呈常染色体隐性遗传模式。在本研究中，我们首次对希腊裔塞浦路斯人群中迄今已识别的所有胱氨酸尿症家族进行了遗传学和临床研究。
通过聚合酶链反应（PCR）单链分析和DNA重测序来发现突变。通过PCR-限制性片段长度多态性分析来研究新的家族。通过医院患者记录和家族分析随访收集临床数据。
我们在属于12个家族的28名希腊裔塞浦路斯胱氨酸尿症患者中总共发现了5种突变。在这28名希腊裔塞浦路斯患者中最常见的突变是SLC3A1-p.T216M，它也是欧洲第二常见的突变，代表了一种遗传奠基者效应。28名患者中有16名是该突变的纯合子。尽管只有一个家族存在明显的近亲通婚圈，但其他患者来自实行了几个世纪内婚制的小村庄的家族。及时的临床和基因诊断并伴有早期治疗，对我们大多数患者的健康状况至关重要。他们中只有约14%发展为慢性肾衰竭，只有一人发展到终末期肾病（ESRD）。
5种SLC3A1和SLC7A9突变似乎是希腊裔塞浦路斯患者胱氨酸尿症遗传基础的病因；致病突变数量如此有限将简化该人群的诊断。
