Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Urolithiasis
Published in: Urolithiasis 5/2015

01-10-2015 | Original Paper

Mutation analysis of SLC3A1 and SLC7A9 genes in patients with cystinuria

Authors: Leila Koulivand, Mehrdad Mohammadi, Behrouz Ezatpour, Rasoul Salehi, Samane Markazi, Sepideh Dashti, Majid Kheirollahi

Published in: Urolithiasis | Issue 5/2015

Login to get access

Abstract

Cystinuria is an autosomal inherited disorder of renal reabsorption of cystine, arginine, lysine, and ornithine. Increased urinary excretion of cystine results in the formation of kidney stones. Considering the few studies on the genetic basis of the cystinuria in the Middle East and the population-specific distribution of mutations in the SLC3A1 and SLC7A9 genes, in the present study, mutation analysis of these two genes was performed in a cohort of Iranian patients with cystinuria. Thirty unrelated cystinuria patients were analyzed for four of the most common mutations using ARMS-PCR (M467T, T216M) and RFLP-PCR (G105R, R333W) methods. For negative sample, two exons of both genes, which harbor many mutations, were subject to DNA sequencing. Eight variants were identified including missense, polymorphism, intron variant, and a novel variant. The most frequent mutations were not detected in our patients and only G105R was found. Since the molecular genetic testing results may influence the therapy and prognosis of cystinuria, this paper contributes to understanding of the molecular basis of cystinuria in the Iranian patients.
Literature
1.
Škopková Z, Hrabincová E, Štástná S, Kozák L, Adam T (2005) Molecular genetic analysis of SLC3A1 and SLC7A9 genes in Czech and Slovak cystinuric patients. Ann Hum Genet 69:501–507CrossRefPubMed
2.
Yuen Y, Lam C, Lai C, Tong S, Li P, Tam S, Kwan EY, Chan S, Tsang W, Chan K (2006) Heterogeneous mutations in the SLC3A1 and SLC7A9 genes in Chinese patients with cystinuria. Kidney Int 69:123–128CrossRefPubMed
3.
Popovska-Jankovic K, Tasic V, Bogdanovic R, Miljkovic P, Baskin E, Efremov G, Plaseska-Karanfilska D (2009) Five novel mutations in cystinuria genes SLC3A1 and SLC7A9. Balk J Med Gen 12:15–20
4.
Chillarón J, Font-Llitjós M, Fort J, Zorzano A, Goldfarb DS, Nunes V, Palacín M (2010) Pathophysiology and treatment of cystinuria. Nat Rev Neurol 6:424–434CrossRef
5.
Kummer S, Venghaus A, Schlune A, Leube B, Eggermann T, Spiekerkoetter U (2014) Synergistic mutations in SLC3A1 and SLC7A9 leading to heterogeneous cystinuria phenotypes: pitfalls in the diagnostic workup. Pediatr Nephrol 29:155–159CrossRefPubMed
6.
Tanzer F, Ozgur A, Bardakci F (2007) Type I cystinuria and its genetic basis in a population of Turkish school children. Int J Urol 14:914–917CrossRefPubMed
7.
Saravakos P, Kokkinou V, Giannatos E (2014) Cystinuria: current diagnosis and management. Urology 83:693–699CrossRefPubMed
8.
Akhavan sepahi M, Sharifian M, Shajari A, Heidary A (2009) Clinical manifestations and etiology of renal and urethra stone in children less than 14 years old referring to Fatemi-e-Sahamieh pediatric hospital in Qom, 2007-2008. Arak Univ Med Sci J 12:1–7
9.
Calonge MJ, Gasparini P, Chillarón J, Chillón M, Gallucci M, Rousaud F, Zelante L, Testar X, Dallapiccola B, Di Silverio F (1994) Cystinuria caused by mutations in rBAT, a gene involved in the transport of cystine. Nat Genet 6:420–425CrossRefPubMed
10.
Feliubadaló L, Font M, Purroy J, Rousaud F, Estivill X, Nunes V, Golomb E, Centola M, Aksentijevich I, Kreiss Y (1999) Non-type I cystinuria caused by mutations in SLC7A9, encoding a subunit (b0,+AT) of rBAT. Nat Genet 23:52–57PubMed
11.
Schmidt C, Vester U, Hesse A, Lahme S, Lang F, Zerres K, Eggermann T (2004) The population-specific distribution and frequencies of genomic variants in the SLC3A1 and SLC7A9 genes and their application in molecular genetic testing of cystinuria. Urol Res 32:75–78CrossRefPubMed
12.
Font M, Feliubadaló L, Estivill X, Nunes V, Golomb E, Kreiss Y, Pras E, Bisceglia L, d’Adamo AP, Zelante L (2001) Functional analysis of mutations in SLC7A9, and genotype–phenotype correlation in non-Type I cystinuria. Hum Mol Genet 10:305–316CrossRefPubMed
13.
Eggermann T, Spengler S, Wirth J, Lahme S (2011) Molecular genetic testing in cystinuria. Int J Hum Genet 11:41–44
14.
Egoshi K-I, Akakura K, Kodama T, Ito H (2000) Identification of five novel SLC3A1 (rBAT) gene mutations in Japanese cystinuria. Kidney Int 57:25–32CrossRefPubMed
15.
Eggermann T, Venghaus A, Zerres K (2012) Cystinuria: an inborn cause of urolithiasis. Orphanet J Rare Dis 7:1–11CrossRef
16.
Kheradpir MH, Bodaghi E (1990) Childhood urolithiasis in Iran with special reference to staghorn calculi. Urol Int 45:99–103CrossRefPubMed
17.
Koulivand L, Mohammadi M, Ezatpour B, Kheirollahi M (2015) Cystinuria in a patient with a novel mutation in SLC7A9 gene. Iran J Kidney Dis 9:63–66PubMed
18.
Botzenhart E, Vester U, Schmidt C, Hesse A, Halber M, Wagner C, Lang F, Hoyer P, Zerres K, Eggermann T (2002) Cystinuria in children: distribution and frequencies of mutations in the SLC3A1 and SLC7A9 genes. Kidney Int 62:1136–1142CrossRefPubMed
19.
Chatzikyriakidou A, Sofikitis N, Georgiou I (2005) Identification of novel cystinuria mutations and polymorphisms in SLC3A1 and SLC7A9 genes: absence of SLC7A10 gene mutations in cystinuric patients. Genet Test 9:175–184CrossRefPubMed
20.
Shigeta Y, Kanai Y, Chairoungdua A, Ahmed N, Sakamoto S, Matsuo H, Kim D, Fujimura M, Anzai N, Mizoguchi K (2006) A novel missense mutation of SLC7A9 frequent in Japanese cystinuria cases affecting the C-terminus of the transporter. Kidney Int 69:1198–1206CrossRefPubMed
21.
Barbosa M, Lopes A, Mota C, Martins E, Oliveira J, Alves S, De Bonis P, Do Céu Mota M, Dias C, Rodrigues-Santos P (2012) Clinical, biochemical and molecular characterization of Cystinuria in a cohort of 12 patients. Clin Genet 81:47–55CrossRefPubMed
22.
Harnevik L, Fjellstedt E, Molbaek A, Denneberg T, Söderkvist P (2003) Mutation analysis of SLC7A9 in cystinuria patients in Sweden. Genet Test 7:13–20CrossRefPubMed
23.
Chatzikyriakidou A, Sofikitis N, Giannakis D, Tsambalas S, Georgiou I (2004) 466 Six novel polymorphic variants in SLC3A1 and SLC7A9 genes: new approaches to the study of cystinuria. Eur Urol Suppl 3:119CrossRef
24.
Bisceglia L, Calonge MJ, Strologo LD, Rizzoni G, de Sanctis L, Gallucci M, Beccia E, Testar X, Zorzano A, Estivill X (1996) Molecular analysis of the cystinuria disease gene: identification of four new mutations, one large deletion, and one polymorphism. Hum Genet 98:447–451CrossRefPubMed
25.
Schmidt C, Tomiuk J, Botzenhart E, Vester U, Halber M, Hesse A, Wagner C, Lahme S, Lang F, Zerres K (2003) Genetic variations of the SLC7A9 gene: allele distribution of 13 polymorphic sites in German cystinuria patients and controls. Clin Nephrol 59:353–359PubMed
26.
Chatzikyriakidou A, Sofikitis N, Kalfakakou V, Siamopoulos K, Georgiou I (2006) Evidence for association of SLC7A9 gene haplotypes with cystinuria manifestation in SLC7A9 mutation carriers. Urol Res 34:299–303CrossRefPubMed
27.
Harnevik L, Fjellstedt E, Molbæk A, Tiselius HG, Denneberg T, Söderkvist P (2001) Identification of 12 novel mutations in the SLC3A1 gene in Swedish cystinuria patients. Hum Mutat 18:516–525CrossRefPubMed
28.
Gasparini P, Calonge MJ, Bisceglia L, Purroy J, Dianzani I, Notarangelo A, Rousaud F, Gallucci M, Testar X, Ponzone A (1995) Molecular genetics of cystinuria: identification of four new mutations and seven polymorphisms, and evidence for genetic heterogeneity. Am J Hum Genet 57:781PubMedCentralPubMed
29.
Chatzikyriakidou A, Louizou E, Dedousis GV, Bisceglia L, Michelakakis H, Georgiou I (2008) An overview of SLC3A1 and SLC7A9 mutations in Greek cystinuria patients. Mol Genet Metab 95:192–193CrossRefPubMed
30.
Brauers E, Hozyasz K, Golabek B, Slowik M, Schmidt C, Vester U, Zerres K, Eggermann T (2006) Identification of novel cystinuria mutations in pediatric patients. J Pediatr Uorol 2:575–578CrossRef
31.
Endsley JK, Phillips JA III, Hruska KA, Denneberg T, Carlson J, George AL Jr (1997) Genomic organization of a human cystine transporter gene (SLC3A1) and identification of novel mutations causing cystinuria. Kidney Int 51:1893–1899CrossRefPubMed
32.
Gitomer WL, Reed BY, Ruml LA, Sakhaee K, Pak CY (1998) Mutations in the genomic deoxyribonucleic acid for SLC3A1 in patients with cystinuria 1. J Clin Endocr Metab 83:3688–3694PubMed
Metadata
Title
Mutation analysis of SLC3A1 and SLC7A9 genes in patients with cystinuria
Authors
Leila Koulivand
Mehrdad Mohammadi
Behrouz Ezatpour
Rasoul Salehi
Samane Markazi
Sepideh Dashti
Majid Kheirollahi
Publication date
01-10-2015
Publisher
Springer Berlin Heidelberg
Published in
Urolithiasis / Issue 5/2015
Print ISSN: 2194-7228
Electronic ISSN: 2194-7236
DOI
https://doi.org/10.1007/s00240-015-0794-0

Other articles of this Issue 5/2015

Urolithiasis 5/2015 Go to the issue

Original Paper

Antilithic effects of extracts from different polarity fractions of Desmodium styracifolium on experimentally induced urolithiasis in rats

Original Paper

Clinical factors prolonging the operative time of flexible ureteroscopy for renal stones: a single-center analysis

Original Paper

High frequency of SLC22A12 variants causing renal hypouricemia 1 in the Czech and Slovak Roma population; simple and rapid detection method by allele-specific polymerase chain reaction

Original Paper

Age-related delay in urinary stone clearance in elderly patients with solitary proximal ureteral calculi treated by extracorporeal shock wave lithotripsy

Original Paper

The efficacy and safety of percutaneous nephrolithotomy under general versus regional anesthesia: a systematic review and meta-analysis

Original Paper

Calcium oxalate calculi-induced clusterin expression in kidney