Sedoheptulokinase deficiency due to a 57-kb deletion in cystinosis patients causes urinary accumulation of sedoheptulose: elucidation of the CARKL gene
✍ Scribed by 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
- Book ID
- 102262061
- Publisher
- John Wiley and Sons
- Year
- 2008
- Tongue
- English
- Weight
- 183 KB
- Volume
- 29
- Category
- Article
- ISSN
- 1059-7794
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✦ Synopsis
Communicated by Johannes Zschocke
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 o9) and erythritol (234-1110 mmol/mol creatinine; controls and other cystinosis patients o148). 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 1 ATPsedoheptulose-7-phosphate 1 ADP and that deletion of CARKL causes urinary accumulation of sedoheptulose and erythritol. Hum Mutat 29(4), 532-536, 2008.