Identification of 14 novel CTNS mutations and characterization of seven splice site mutations associated with cystinosis
- PMID:12442267
- DOI: 10.1002/humu.10141
Identification of 14 novel CTNS mutations and characterization of seven splice site mutations associated with cystinosis
Abstract
Cystinosis is an autosomal recessive disorder characterized by intra-lysosomal accumulation of cystine. Three disease forms exist, infantile, juvenile, and ocular nonnephropathic cystinosis, delineated on the basis of severity of symptoms and age of onset. Mutations in the causative gene, CTNS, which encodes cystinosin, the seven transmembrane domain lysosomal cystine transporter, have been identified in all forms confirming their allelic status. By screening for mutations in the CTNS exons and promotor region, we report 14 novel mutations associated with cystinosis: 11 underlying infantile cystinosis, two juvenile cystinosis, and one associated with an atypical form of the disease. These mutations, all situated in the exons or immediately flanking intronic sequences, comprise in-frame insertions and deletions, as well as missense, nonsense, and putative splice-site mutations. Furthermore, we confirmed the putative splice-site mutations we have reported to date (five novel and two previously reported) by isolation of RNA from the affected carriers and characterization of the resultant transcripts using RT-PCR. Since the cloning of CTNS, we have screened for mutations in 108 affected individuals, which has resulted in a high mutation detection rate of 95.8%. Interestingly, the few undetectable mono- or bi-allelic mutations segregated mostly in the noninfantile forms, suggesting that these individuals carry mutations either in the introns or in unidentified regulatory sequences.
Copyright 2002 Wiley-Liss, Inc.
Similar articles
- Molecular pathogenesis of cystinosis: effect of CTNS mutations on the transport activity and subcellular localization of cystinosin.Kalatzis V, Nevo N, Cherqui S, Gasnier B, Antignac C.Kalatzis V, et al.Hum Mol Genet. 2004 Jul 1;13(13):1361-71. doi: 10.1093/hmg/ddh152. Epub 2004 May 5.Hum Mol Genet. 2004.PMID:15128704
- CTNS mutations in patients with cystinosis.Anikster Y, Shotelersuk V, Gahl WA.Anikster Y, et al.Hum Mutat. 1999;14(6):454-8. doi: 10.1002/(SICI)1098-1004(199912)14:6<454::AID-HUMU2>3.0.CO;2-H.Hum Mutat. 1999.PMID:10571941Review.
- Analysis of the CTNS gene in patients of German and Swiss origin with nephropathic cystinosis.Kiehntopf M, Schickel J, Gönne Bv, Koch HG, Superti-Furga A, Steinmann B, Deufel T, Harms E.Kiehntopf M, et al.Hum Mutat. 2002 Sep;20(3):237. doi: 10.1002/humu.9063.Hum Mutat. 2002.PMID:12204010
- Characterization of CTNS mutations in Arab patients with cystinosis.Aldahmesh MA, Humeidan A, Almojalli HA, Khan AO, Rajab M, AL-Abbad AA, Meyer BF, Alkuraya FS.Aldahmesh MA, et al.Ophthalmic Genet. 2009 Dec;30(4):185-9. doi: 10.3109/13816810903200953.Ophthalmic Genet. 2009.PMID:19852576
- [From gene to disease: cystinosis].Levtchenko EN, Wilmer M, de Graaf-Hess AC, van den Heuvel LP, Blom H, Monnens LA.Levtchenko EN, et al.Ned Tijdschr Geneeskd. 2004 Mar 6;148(10):476-8.Ned Tijdschr Geneeskd. 2004.PMID:15042893Review.Dutch.
Cited by
- A randomized controlled crossover trial with delayed-release cysteamine bitartrate in nephropathic cystinosis: effectiveness on white blood cell cystine levels and comparison of safety.Langman CB, Greenbaum LA, Sarwal M, Grimm P, Niaudet P, Deschênes G, Cornelissen E, Morin D, Cochat P, Matossian D, Gaillard S, Bagger MJ, Rioux P.Langman CB, et al.Clin J Am Soc Nephrol. 2012 Jul;7(7):1112-20. doi: 10.2215/CJN.12321211. Epub 2012 May 3.Clin J Am Soc Nephrol. 2012.PMID:22554716Free PMC article.Clinical Trial.
- New aspects of the pathogenesis of cystinosis.Kalatzis V, Antignac C.Kalatzis V, et al.Pediatr Nephrol. 2003 Mar;18(3):207-15. doi: 10.1007/s00467-003-1077-5. Epub 2003 Feb 27.Pediatr Nephrol. 2003.PMID:12644911Review.
- Genetic basis of cystinosis in Turkish patients: a single-center experience.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.Topaloglu R, et al.Pediatr Nephrol. 2012 Jan;27(1):115-21. doi: 10.1007/s00467-011-1942-6. Epub 2011 Jul 24.Pediatr Nephrol. 2012.PMID:21786142Free PMC article.
- Residual Cystine Transport Activity for Specific Infantile and JuvenileCTNS Mutations in a PTEC-Based Addback Model.Medaer L, David D, Smits M, Levtchenko E, Sampaolesi M, Gijsbers R.Medaer L, et al.Cells. 2024 Apr 6;13(7):646. doi: 10.3390/cells13070646.Cells. 2024.PMID:38607085Free PMC article.
- Intellectual and motor performance, quality of life and psychosocial adjustment in children with cystinosis.Ulmer FF, Landolt MA, Vinh RH, Huisman TA, Neuhaus TJ, Latal B, Laube GF.Ulmer FF, et al.Pediatr Nephrol. 2009 Jul;24(7):1371-8. doi: 10.1007/s00467-009-1149-2. Epub 2009 Mar 18.Pediatr Nephrol. 2009.PMID:19294426
Publication types
MeSH terms
Substances
Related information
LinkOut - more resources
Full Text Sources
Molecular Biology Databases