A Novel Variant in Iranian Patient with Cystinuria: A Case Report

Cystinuria is an autosomal recessive disorder in which the renal reabsorption of cystine, arginine, lysine and ornithine are disturbed. The two genes, the pathogenic forms of which are responsible for the disorder, are SLC7A9 and SLC3A1. In this study, we describe a disease that has a new c.916A> T variant (p. K306 *) in exon 5 of the SLC3A1 gene. This variant results in the NMD phenomenon in which the protein product is not produced because of mRNA destruction. In 2020, blood sample of a 41-yr-old man from east Azerbaijan, Iran together with his parents were collected to be studied. PCR and direct sequencing were performed to detect the possible SLC3A1 variant. Whole-gene sequence analysis done by Mutation surveyor Software revealed a novel nonsense homozygous variant in exon 5 of the gene. Parental Sequence Analysis shows that they are heterozygous. According to ACMG guideline, this variant is considered as pathogen. Finding serious mutations can allow rapid screening for cystinuria by analyzing common mutations. It should also be considered as a pathogenic variant in patients’ cystinuria.

Five Novel Mutations in Cystinuria Genes SLC3A1 and SLC7A9

Five Novel Mutations in Cystinuria Genes SLC3A1 and SLC7A9Cystinuria is an autosomal recessive disorder that is characterized by impaired transport of cystine, lysine, ornithine and arginine in the proximal renal tubule and epithelial cells of the gastrointestinal tract. The transport of these amino acids is mediated by the rBAT/b0,+AT transporter, the subunits of which are encoded by the genes SLC3A1, located on chromosome 2p16.3-21, and SLC7A9, located on chromosome 19q12-13.1. Based on the urinary cystine excretion patterns of obligate heterozygotes, cystinuria is classified into type I (normal amino acid urinary pattern in heterozygotes) and non type I (a variable degree of urinary hyper excretion of cystine and dibasic amino acids in heterozygotes). On the basis of genetic aspects, cystinuria is classified into type A, is caused by mutations in both alleles of SLC3A1; type B, caused by mutations in both alleles of SLC7A9 and type AB, is caused by one mutation in SLC3A1 and one mutation in SLC7A9. Here we present two novel mutations in the SLC3A1 gene (C242R and L573X), which were found in patients from Serbia, and three in the SLC7A9 gene (G73R, V375I, 1048-1051 delACTC), found in patients from Serbia, Macedonia and Turkey, respectively.