Genetic study and clinical presentation in patients with cystinuria in the childhood age group

Purpose: In this study, it was aimed to determine the genetic diversity in the follow-up patients with the diagnosis of cystinuria starting in the childhood age group and to evaluate the effect of the genetics clinic. It was also aimed to determine the relationship between the genetic structures of the patients and the course and prognosis of the disease to contribute to the related literature. Material and Methods: This study was carried out between February 2017 and February 2018 at Çukurova University Faculty of Medicine Department of Pediatric Nephrology. In the first stage of the study; the files of 62 patients who were diagnosed as cystinuria starting in childhood between 2000-2018 were examined retrospectively and their characteristic data were analyzed. In the second stage of the study; 31 volunteer patients with cystinuria were identified for blood donation, urine collection and genetic analysis. Blood samples were taken from all of the patients for biochemical evaluation and genetic analysis in terms of renal calculi etiology. 24-hour urine samples were collected from the same patients and urine biochemical analyzes were performed on those samples. Analysis were done at Çukurova University Faculty of Medicine Department of Genetics through two gene sequence analysis and sanger sequencing method. Upon the obtained data, statistical analysis was carried out at Çukurova University Faculty of Medicine Biostatistics Department. Findings: While 15 known mutations that are known for SLC3A1 and SLC7A9 genes were detected in 31 patients who were being monitored by us with cystinuria diagnosis; polymorphism was observed in 16 patients. No new mutations were detected. No statistically significant differences were found between these two groups having mutation and polymorphism variants when they were compared in terms of urinary cysteine excretion, renal function and other urine biochemical parameters together with clinical onset age, drug use, initial symptoms and operative history. In the comparison of the groups carrying SLC3A1 and SLC7A9 mutations, cysteine excretion and the rates of the urinary cystine to creatinine in the 24-hour urine were found significantly higher in the SLC3A1 group. No significant difference was found in other parameters. Conclusion: In our study, urinary cystine excretion of patients was found significantly higher despite the treatment. In the genetic analysis of patients, polymorphism was detected in a group with a high rate of 51.6% (16/31). These sixteen patients in which any known mutations of the SLC3A1 and SLC7A9 genes which are known in cystinuria etiology were not detected were evaluated with their clinics. When evaluated together with the literature, polymorphism variants were not directly associated as disease factors but they were associated with disease susceptibility in 16 patients (51.6%) who had recurrent renal calculi formation, severe clinical course but no pathogenic mutation. It was also thought some other genes existed which might be responsible for the disease. Moreover, it was also seen that further studies are needed under the leadership of this study which is the first in our region. Key words: Cystinuria, genetic analysis, sanger sequencing, SLC3A1, SLC7A9