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Pediatric Nephrology
Published in: Pediatric Nephrology 4/2015

01-04-2015 | Original Article

Common mutation causes cystinosis in the majority of black South African patients

Authors: E. Patricia Owen, Jenisha Nandhlal, Felicity Leisegang, George Van der Watt, Peter Nourse, Priya Gajjar

Published in: Pediatric Nephrology | Issue 4/2015

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Abstract

Background

The mutations responsible for cystinosis in South African patients are currently unknown. A pertinent question is whether they are similar to those described elsewhere in the world.

Methods

Children who were being managed for cystinosis in the Western Cape Province of South Africa between 2002 and 2013 were studied. All underwent molecular analysis to detect sequence variations in the cystinosis gene.

Results

This cohort study included 20 patients, 13 of whom were Xhosa-speaking black South Africans and seven were Cape Coloureds (mixed race); none were Caucasian. All had nephropathic infantile-type cystinosis with evidence of proximal tubulopathy, with glycosuria and renal phosphate wasting. Diagnosis was confirmed in 19 cases by demonstrating an elevated cystine concentration in leukocytes. Molecular analysis of the cystinosin gene revealed that 19 patients had a G > A mutation in intron 11 (CTNS-c.971-12G > A p.D324AfsX44) which caused an out-of-frame 10-bp insertion. Of these 19 patients, 16 were homozygous for this mutation, which was the most frequent mutation identified in the alleles of the black South African and Cape Coloured patients (96 and 71 %, respectively).

Conclusion

We recommend that black South African and Cape Coloured patients presenting with cystinosis be tested for CTNS-c.971-12G > A in the first instance, with the possibility of prenatal testing being offered to at-risk families.
Literature
1.
Gahl WA, Bashan N, Tietze F, Bernardini I, Schulman JD (1982) Cystine transport is defective in isolated leukocyte lysosomes from patients with cystinosis. Science 217:1263–1265CrossRefPubMed
2.
3.
Gahl WA, Balog JZ, Kleta R (2007) Nephropathic cystinosis in adults: natural history and effects of oral cysteamine therapy. Ann Intern Med 147:242–250CrossRefPubMed
4.
Gahl WA, Reed GF, Thoene JG, Schulman JD, Rizzo WB, Jonas AJ, Denman DW, Schlesselman JJ, Corden BJ, Schneider JA (1987) Cysteamine therapy for children with nephropathic cystinosis. N Engl J Med 316:971–977CrossRefPubMed
5.
Stenson PD, Ball EV, Mort M, Phillips AD, Shiel JA, Thomas NS, Abeysinghe S, Krawczak M, Cooper DN (2003) The human gene mutation database (HGMD®): 2003 update. Hum Mutat 21:577–581CrossRefPubMed
6.
Topaloglu R, Vilboux T, Coskun T, Ozaltin F, Tinloy B, Gunay-Aygun M, Bakkaloglu A, Besbas N, van den Heuvel L, Kleta R, Gahl WA (2012) Genetic basis of cystinosis in Turkish patients:a single-center experience. Pediatr Nephrol 27:115–121CrossRefPubMedCentralPubMed
7.
Yeetong P, Tongkobpetch S, Kingwatanakul P, Deekajorndech T, Bernardini IM, Suphapeetiporn K, Gahl WA, Shotelersuk V (2012) Two novel CTNS mutations in cystinosis patients in Thailand. Gene 499(2):323–325CrossRefPubMedCentralPubMed
8.
Shahkarami S, Galehdari H, Ahmadzadeh A, Babaahmadi M, Pedram M (2013) The first molecular genetics analysis of individuals suffering from nephropathic cystinosis in the southwestern Iran. Nefrologia 33(3):308–315PubMed
9.
Shotelersuk V, Larson D, Anikster Y, McDowell G, Lemons R, Bernardini I, Guo J, Thoene J, Gahl WA (1998) CTNS mutations in an American-based population of cystinosis patients. Am J Hum Genet 63:1352–1362CrossRefPubMedCentralPubMed
10.
McGowan-Jordan J, Stoddard KLP, Orrbine E, McLaine P, Town M, Goodyer P, MacKenzie A, Heick H (1999) Molecular analysis of cystinosis: probable Irish origin of the most common french Canadian mutation. Eur J Hum Genet 7:671–678CrossRefPubMed
11.
Kalatzis V, Cherqui S, Jean G, Cordier B, Cochat P, Broyer M, Antignac C (2001) Characterization of a putative founder mutation that accounts for the high incidence of cystinosis in Brittany. J Am Soc Nephrol 12:2170–2174PubMed
12.
Kleta R, Anikster Y, Lucero C, Shotelersuk V, Huizing M, Bernardini I, Park M, Thoene J, Schneider J, Gahl WA (2001) CTNS mutations in African American patients with cystinosis. Mol Genet Metab 74:332–337CrossRefPubMed
13.
14.
Patterson N, Petersen DC, van der Ross RE, Sudoyo H, Glashoff RH, Marzuki S, Reich D, Hayes VM (2009) Genetic structure of a unique admixed population: implications for medical research. Hum Mol Genet 19:411–419CrossRefPubMed
15.
Anikster Y, Lucero C, Touchmann JW, Huizing M, McDowell G, Shotelersuk V, Green ED, Gahl WA (1999) Identification and detection of the common 65-kb deletion breakpoint in the nephropathic cystinosis gene (CTNS). Mol Genet Metab 66:111–116CrossRefPubMed
16.
Town M, Jean G, Cherqui S, Attard M, Forestier L, Whitmore SA, Callen DF, Gribouval O, Broyer M, Bates GP, van’t Hoff W, Antignac C (1998) A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis. Nat Genet 18(4):319–324CrossRefPubMed
17.
Macías-Vidal J, Rodés M, Hernández-Pérez JM, Vilaseca MA, Coll MJ (2009) Analysis of the CTNS gene in 32 cystinosis patients from Spain. Clin Genet 76:486–489CrossRefPubMed
18.
Kaletzis V, Nevo N, Cherqui S, Gasnier B, Antignac C (2004) Molecular pathogenesis of cystinosis: effect of CTNS mutations on the transport activity and subcellular localization of cystinosin. Hum Mol Genet 13:1361–1371CrossRef
19.
The 1000 Genomes Project Consortium (2012). An integrated map of genetic variation from 1,092 human genomes. Nature 491:56–65
20.
Geer LY, Marchler-Bauer A, Geer RC, Han L, He J, He S, Liu C, Shi W, Bryant SH (2010) The NCBI BioSystems database. Nucleic Acids Res 38:492–496CrossRef
21.
Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, Kondrashov AS, Sunyaev SR (2010) A method and server for predicting damaging missense mutations. Nat Methods 7(4):248–249CrossRefPubMedCentralPubMed
22.
Attard M, Jean G, Forestier L, Cherqui S, van’t Hoff W, Broyer M, Antignac C, Town M (1999) Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin. Hum Mol Genet 8:2507–2514CrossRefPubMed
23.
Kalatzis V, Cohen-Solal L, Cordier B, Frishberg Y, Kemper M, Nuutinen EM, Legrand E, Cochat P, Antignac C (2002) Identification of 14 novel CTNS mutations and characterization of seven splice site mutations associated with cystinosis. Hum Mutat 20:439–446CrossRefPubMed
24.
Kersey PJ, Staines DM, Lawson D, Kulesha E, Derwent P, Humphrey JC, Hughes DS, Keenan S, Kerhornou A, Koscielny G, Langridge N, McDowall MD, Megy K, Maheswari U, Nuhn M, Paulini M, Pedro H, Toneva I, Wilson D, Yates A, Birney E (2011) Ensembl genomes: an integrative resource for genome-scale data from non-vertebrate species. Nucleic Acids Res 40(D1):D91–D97CrossRefPubMedCentralPubMed
25.
26.
Henderson H, Leisegang F, Brown R, Eley B (2002) The clinical and molecular spectrum of galactosemia in patients from the Cape Town region of South Africa. BMC Pediatr 2:7CrossRefPubMedCentralPubMed
27.
Arndt S, Heitner R, Lane A, Ramsay M (2009) Gluco cerebrosidase gene mutations in black South Africans with Gaucher disease. Blood Cells Mol Dis 43(1):129–33CrossRefPubMed
28.
Van der Watt G, Owen EP, Berman P, Meldau S, Watermeyer N, Olpin SE, Manning NJ, Baumgarten I, Leisegang F, Henderson H (2010) Glutaric aciduria type 1 in South Africa—high incidence of glutaryl-CoA dehydrogenase deficiency in black South Africans. Mol Genet Metab 101:178–182CrossRefPubMed
29.
Owen EP, Leisegang F, Whitelaw A, Simpson J, Baker S, Würzner R, Potter P, Orren A (2010) Complement component C5 and C6 mutation screening indicated in meningococcal disease in South Africa. S Afr Med J 102(6):525–527
30.
Metadata
Title
Common mutation causes cystinosis in the majority of black South African patients
Authors
E. Patricia Owen
Jenisha Nandhlal
Felicity Leisegang
George Van der Watt
Peter Nourse
Priya Gajjar
Publication date
01-04-2015
Publisher
Springer Berlin Heidelberg
Published in
Pediatric Nephrology / Issue 4/2015
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-014-2980-7

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