Presentation Authors: Sabrina Reis*, Ruan Pimenta, Giovanni Marchini, Katia Leite, Nayara Viana, William Simoes, Fabio Torricelli, Fabio Vicentini, Alexandre Danilovic, William Nahas, Miguel Srougi, Eduardo Mazzucchi, Sao Paulo, Brazil
Introduction: Cystinuria is a recessive inherited disorder characterized by impaired tubular reabsorption of cystine and dibasic amino acids ultimately resulting in urolithiasis. Previous studies have shown mutations in SLC3A1 gene associated with type A cystinuria that follows a complete recessive inheritance in half of the cases. The other half has been related to mutations in the SLC7A9 gene considered responsible for cystinuria type B presumably inherited by an incomplete dominant manner. Considering the paucity of studies on the genetic basis of cystinuria, we have mapped genetic mutations of a Brazilian family affected by the disease. Two members of the family presented with severe disease very early in life. Our aim was to validate the described mutations in genes SLC3A1 and SLC7A9, and to look for new alterations that may be associated to the development of cystinuria in our population.
Methods: PCR analysis of SLC7A9 and SLC3A1 genes was performed using DNA samples from peripheral whole blood cells of five members from the same family (figure 1). After amplification the samples were sequenced in the 3730 DNA Analyzer (Applied Biossystems).
Results: Six different mutations were identified in SLC7A9 gene: three missense mutations and three synonym mutation (table 1). The mother who presents a non-severe form of cystinuria has six mutations, all in heterozygosis. The father and one daughter have not any manifestation of the disease. The son and the other daughter who have a severe form of cystinuria have all the six mutations in homozygous. SLC3A1 showed one mutation in homozygous and both siblings affected by the disease presented this mutation
Conclusions: We have shown that six different mutations in SLC7A9 are responsible for the manifestation of cystinuria, and the homozygous is related to severe and early development of urolithiasis.
Source of Funding: FAPESP 2017/12742-2