Sedoheptulokinase deficiency due to a 57-kb deletion in cystinosis patients causes urinary accumulation of sedoheptulose: elucidation of the CARKL gene.
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| Abstract |
The most common mutation in the nephropathic cystinosis (CTNS) gene is a homozygous 57-kb deletion that also includes an adjacent gene carbohydrate kinase-like (CARKL). The latter gene encodes a protein that is predicted to function as a carbohydrate kinase. Cystinosis patients with the common 57-kb deletion had strongly elevated urinary concentrations of sedoheptulose (28-451 mmol/mol creatinine; controls and other cystinosis patients <9) and erythritol (234-1110 mmol/mol creatinine; controls and other cystinosis patients <148). Enzyme studies performed on fibroblast homogenates derived from patients carrying the 57-kb deletion revealed 80% reduction in their sedoheptulose phosphorylating activity compared to cystinosis patients with other mutations and controls. This indicates that the CARKL-encoded protein, sedoheptulokinase (SHK), is responsible for the reaction: sedoheptulose + ATP --> sedoheptulose-7-phosphate + ADP and that deletion of CARKL causes urinary accumulation of sedoheptulose and erythritol.
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| Authors | Mirjam M C Wamelink, Eduard A Struys, Erwin E W Jansen, Elena N Levtchenko, Fokje S M Zijlstra, Udo Engelke, Henk J Blom, Cornelis Jakobs, Ron A Wevers |
| Journal | Human mutation (Hum Mutat) Vol. 29 Issue 4 Pg. 532-6 (Apr 2008) ISSN: 1098-1004 [Electronic] United States |
| PMID | 18186520 (Publication Type: Journal Article) |
| Copyright | Copyright 2008 Wiley-Liss, Inc. |
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