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INTRODUCTION AND OBJECTIVE: Cystinuria is a rare genetic cause for kidney stones. Mutations have been found in two genes, SLC3A1 and SLC7A9, on chromosome 2 and 19 respectively, which code for the two subunits of the amino acid transport system, RBAT and b 0,þ AT in the renal proximal tubule and the small intestine. In the literature, cystinuria has been previously defined as an autosomal recessive disorder, however, some heterozygous patients present with symptoms of the disease. There is controversy about whether these patients are carriers or true cystinurics.METHODS: We studied the correlation between the genotype and phenotype in our cohort of SLC7A9 heterozygotes in a single center. Phenotype was recorded including: urine cystine levels, calculus analysis, cytology, previous procedures, active and past medications, medical and family history. These were then compared between patients and used to identify which ones were symptomatic.RESULTS: From a database of 184 genotyped cystinuric patients 20(10.9%) were identified as SLC7A9 heterozygote. The most common mutation in SLC7A9 was c.614dupA which was expressed in 5(25%) patients. This was also a common mutation for all 66 patients in the database with a mutation in SLC7A9 (13(19.7%)). 6(30%) patients, had a documented proven cystine stone on analysis; 9(45%) had cystine crystals on cytology; 5(25%) were positive for both. Additionally 13(55%) patients had an elevated urine cystine value above 100 mM/M creatinine. In all, 13(65%) patients were classified as having a clinical diagnosis of cystinuria; of these 13 patients: 12(92.3%) had undergone at least one stone-related procedure with 8(61.5%) having more than one procedure, 2(15.4%) are currently actively taking medication for cystinuria (alkalinisation or chelating agent), and 4(30.7%) have relatives with stone episodes. 1 patient did not have a clinical diagnosis of cystinuria. 6(30%) patients potentially do have a diagnosis of cystinuria however this is difficult to confirm as they do not have high urine cystine levels and have no traceable documented stone analysis. Further analysis of future stones is needed as well as genetic analysis with in-depth exome sequencing to look for other responsible genes, to establish if they have the disease or are true carriers.CONCLUSIONS: We have demonstrated the symptomatic presentation of cystinuria in patients heterozygous for SLC7A9 who previously would have been classified as carriers. This suggests that the inheritance of SLC7A9 is autosomal dominant with incomplete penetrance but further work is needed to fully characterise this phenotype.

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Carrijo et al. Grande trombo fixo entre átrios Relato de Caso Carrijo et al. Grande trombo fixo entre átriosVídeos 1 e 2 -Ecocardiograma transtorácico com imagem hipoecóica com hipermobilidade na cavidade atrial esquerda e direita, estendendo-se para os ventrículos esquerdo e direito, respectivamente.