Health Conditions Related to Genetic Changes
DOLK-congenital disorder of glycosylation
At least six mutations in the DOLK gene have been found to cause DOLK-congenital disorder of glycosylation (DOLK-CDG, formerly known as congenital disorder of glycosylation type Im). This condition often causes the heart to be weakened and enlarged (dilated cardiomyopathy), but it can also result in neurological problems as well as other signs and symptoms.
DOLK gene mutations change single protein building blocks (amino acids) in the dolichol kinase enzyme, leading to an enzyme with reduced or absent activity. Without properly functioning dolichol kinase, dolichol phosphate is not produced and glycosylation cannot proceed normally. In particular, a protein known to stabilize heart muscle fibers, called alpha-dystroglycan, has been shown to have reduced glycosylation in people with DOLK-CDG. Impaired glycosylation of alpha-dystroglycan disrupts its normal function, which damages heart muscle fibers as they repeatedly contract and relax. Over time, the fibers weaken and break down, leading to dilated cardiomyopathy. The other signs and symptoms of DOLK-CDG are likely due to the abnormal glycosylation of additional proteins in other organs and tissues.
More About This Health ConditionOther Names for This Gene
- CDG1M
- DK
- DK1
- dolichol kinase 1
- KIAA1094
- SEC59
- SEC59 homolog
- TMEM15
- transmembrane protein 15
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Buczkowska A, Swiezewska E, Lefeber DJ. Genetic defects in dolichol metabolism. J Inherit Metab Dis. 2015 Jan;38(1):157-69. doi: 10.1007/s10545-014-9760-1. Epub 2014 Oct 1. Citation on PubMed or Free article on PubMed Central
- Denecke J, Kranz C. Hypoglycosylation due to dolichol metabolism defects. Biochim Biophys Acta. 2009 Sep;1792(9):888-95. doi: 10.1016/j.bbadis.2009.01.013. Epub 2009 Feb 3. Citation on PubMed
- Shridas P, Waechter CJ. Human dolichol kinase, a polytopic endoplasmic reticulum membrane protein with a cytoplasmically oriented CTP-binding site. J Biol Chem. 2006 Oct 20;281(42):31696-704. doi: 10.1074/jbc.M604087200. Epub 2006 Aug 21. Citation on PubMed
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