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Pathway Description
Cystinosis, Ocular Nonnephropathic
Mus musculus
Category:
Metabolite Pathway
Sub-Category:
Disease
Created: 2018-09-10
Last Updated: 2019-09-15
Ocular non-nephropathic cystinosis, also known as adult-onset cystinosis, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder of the cysteine metabolism pathway. It is caused by a defect in the CTNS gene, which encodes the protein cystinosin, which acts as a cystine/H+ symporter that transports L-cysteine out of the lysosome. Ocular non-nephropathic cystinosis is characterized by a buildup of cysteine in cells, in the case of this form in the cornea. Symptoms include photophobia and damage to the cornea due to crystals forming from the excess cysteine. However, unlike other forms of cystinosis, no or minimal kidney damage occurs. Treatment with cysteamine, a drug that can convert cysteine into a form that can be secreted by the lysosome, can be effective in all of the forms of cystinosis. It is estimated that ocular non-nephropathic cystinosis affects less than 1 in 100,000 to 200,000 individuals, which is the rate of the more severe nephropathic cystinosis.
References
Cystinosis, Ocular Nonnephropathic References
Anikster Y, Lucero C, Guo J, Huizing M, Shotelersuk V, Bernardini I, McDowell G, Iwata F, Kaiser-Kupfer MI, Jaffe R, Thoene J, Schneider JA, Gahl WA: Ocular nonnephropathic cystinosis: clinical, biochemical, and molecular correlations. Pediatr Res. 2000 Jan;47(1):17-23.
Pubmed: 10625078
Cherqui S, Sevin C, Hamard G, Kalatzis V, Sich M, Pequignot MO, Gogat K, Abitbol M, Broyer M, Gubler MC, Antignac C: Intralysosomal cystine accumulation in mice lacking cystinosin, the protein defective in cystinosis. Mol Cell Biol. 2002 Nov;22(21):7622-32.
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Cysteine Metabolism References
Lehninger, A.L. Lehninger principles of biochemistry (4th ed.) (2005). New York: W.H Freeman.
Salway, J.G. Metabolism at a glance (3rd ed.) (2004). Alden, Mass.: Blackwell Pub.
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Pubmed: 9223101
Reid LL, Botta D, Lu Y, Gallagher EP, Kavanagh TJ: Molecular cloning and sequencing of the cDNA encoding the catalytic subunit of mouse glutamate-cysteine ligase. Biochim Biophys Acta. 1997 Jun 26;1352(3):233-7. doi: 10.1016/s0167-4781(97)00058-4.
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Reid LL, Botta D, Shao J, Hudson FN, Kavanagh TJ: Molecular cloning and sequencing of the cDNA encoding mouse glutamate-cysteine ligase regulatory subunit. Biochim Biophys Acta. 1997 Aug 7;1353(2):107-10. doi: 10.1016/s0167-4781(97)00092-4.
Pubmed: 9294003
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Pubmed: 16141072
Huttlin EL, Jedrychowski MP, Elias JE, Goswami T, Rad R, Beausoleil SA, Villen J, Haas W, Sowa ME, Gygi SP: A tissue-specific atlas of mouse protein phosphorylation and expression. Cell. 2010 Dec 23;143(7):1174-89. doi: 10.1016/j.cell.2010.12.001.
Pubmed: 21183079
Hirschberger LL, Daval S, Stover PJ, Stipanuk MH: Murine cysteine dioxygenase gene: structural organization, tissue-specific expression and promoter identification. Gene. 2001 Oct 17;277(1-2):153-61. doi: 10.1016/s0378-1119(01)00691-6.
Pubmed: 11602353
Obaru K, Nomiyama H, Shimada K, Nagashima F, Morino Y: Cloning and sequence analysis of mRNA for mouse aspartate aminotransferase isoenzymes. J Biol Chem. 1986 Dec 25;261(36):16976-83.
Pubmed: 3782150
Obaru K, Tsuzuki T, Setoyama C, Shimada K: Structural organization of the mouse aspartate aminotransferase isoenzyme genes. Introns antedate the divergence of cytosolic and mitochondrial isoenzyme genes. J Mol Biol. 1988 Mar 5;200(1):13-22. doi: 10.1016/0022-2836(88)90329-4.
Pubmed: 3379636
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Pubmed: 15038791
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Pubmed: 18948540
Dooley TP, Nair SK, Garcia RE 4th, Courtney BC: Mouse rhodanese gene (Tst): cDNA cloning, sequencing, and recombinant protein expression. Biochem Biophys Res Commun. 1995 Nov 22;216(3):1101-9. doi: 10.1006/bbrc.1995.2734.
Pubmed: 7488186
Cherqui S, Kalatzis V, Forestier L, Poras I, Antignac C: Identification and characterisation of the murine homologue of the gene responsible for cystinosis, Ctns. BMC Genomics. 2000;1:2. doi: 10.1186/1471-2164-1-2. Epub 2000 Dec 6.
Pubmed: 11121245
Chiaverini C, Sillard L, Flori E, Ito S, Briganti S, Wakamatsu K, Fontas E, Berard E, Cailliez M, Cochat P, Foulard M, Guest G, Niaudet P, Picardo M, Bernard FX, Antignac C, Ortonne JP, Ballotti R: Cystinosin is a melanosomal protein that regulates melanin synthesis. FASEB J. 2012 Sep;26(9):3779-89. doi: 10.1096/fj.11-201376. Epub 2012 May 30.
Pubmed: 22649030
This pathway was propagated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0000722
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