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.
2 Pereira D, Schoolwerth AC, Pais VM (2015). Cystinuria: current concepts and future directions. Clin Nephrol , 83(3):138-46.
3 Fazaeli S, Ashouri S, Kheirolahi M, Mohammadi M, Fazilati M (2017). A novel mutation in SLC7A9 gene in cystinuria. Iran J Kidney Dis, 11(2):138-141.
4 Bourderioux M, Nguyen-Khoa T, Chhuon C,et al (2015). A new workflow for proteomic analysis of urinary exosomes and assessment in cystinuria patients. J Proteome Res, 14(1):567-577.
5 Adzhubei I, Jordan DM, Sunyaev SR (2013). Predicting functional effect of human missense mutations using PolyPhen‐2. Curr Protoc Hum Genet, Chapter 7:Unit7.20.
6 Obaid A, Nashabat M, Al Fakeeh K, Al Qahtani AT, Alfadhel M (2017). Delineation of cystinuria in Saudi Arabia: A case series. BMC Nephrol, 18:50.
7 Mikhaylenko D, Prosyannikov M, Baranova A, Nemtsova M (2019). Genetic and Biochemical Features of the Monogenic Hereditary Kidney Stone Disease. Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry, 13(1):1-12.
8 Randall A (1937). The origin and growth of renal calculi. Ann Surg, 105(6):1009-1027.
9 Stenson PD, Mort M, Ball EV,et al (2017). The Human Gene Mutation Database: towards a comprehensive repository of inherited mutation data for medical research, genetic diagnosis and next-generation sequencing studies. Hum Genet, 136(6):665-677.
10 Mizukami K, Raj K, Osborne C, Giger U. (2016). Cystinuria associated with different SLC7A9 gene variants in the cat. PLoS One, 11(7): e0159247.
11 Olschok K, Vester U, Lahme S, Kurth I, Eggermann T (2018). No evidence for point mutations in the novel renal cystine transporter AGT1/SLC7A13 contributing to the etiology of cystinuria. BMC Nephrol, 19(1):278.
12 Endsley JK, Phillips III JA, Hruska KA, et al (1997).Genomic organization of a human cystine transporter gene (SLC3A1) and identification of novel mutations causing cystinuria. Kidney Int, 51 (6):1893-1899.
13 Holbrook JA, Neu-Yilik G, Hentze MW, Kulozik AE (2004). Nonsense-mediated decay approaches the clinic. Nat Genet, 36(8):801-808.
14 Richards S, Aziz N, Bale S, et al (2015). Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genetics In Medicine, 17(5):405-423.
|Issue||Vol 50 No 9 (2021)|
|Cystinuria Kidney stone Iran|
|Rights and permissions|
|This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.|