Dolichol kinase deficiency (DOLK‐CDG): Two new cases and expansion of phenotype
- 17 August 2017
- journal article
- case report
- Published by Wiley in American Journal of Medical Genetics Part A
- Vol. 173 (9), 2428-2434
- https://doi.org/10.1002/ajmg.a.38287
Abstract
Congenital disorders of glycosylation (CDGs) are a group of genetic diseases caused by mutations in genes that are necessary for the addition of oligosaccharides to acceptor proteins or lipids. An early step in this process requires dolichol kinase (DK) to catalyze the formation of dolichyl phosphate, which acts as a membrane anchor for initial attachment of sugar residues that are subsequently built up to oligosaccharides and transferred to acceptor proteins and lipids for further processing. Biallelic mutations in DOLK, the gene for DK, result in human in a CDG with variable symptoms, ranging from nonsyndromic dilated cardiomypopathy to severe multiorgan involvement. We report two female siblings with novel compound heterozygous mutations in DOLK: c.951C>A (p.Tyr317Ter) and c.1558A>G (p.Thr520Ala). Both patients presented in the neonatal period with severe ichthyosis, unusual distal digital constrictions and dilated cardiomyopathy which resulted in death. Histology of the skin showed lipid droplet accumulation in the stratum corneum and keratinocytes, which suggests defective epidermal lipid metabolism. These patients represent an earlier and more severe form of DOLK-CDG (CDG-1m) with a striking presentation at birth that expands the known phenotypic spectrum.Keywords
This publication has 17 references indexed in Scilit:
- Genetic defects in dolichol metabolismJournal of Inherited Metabolic Disease, 2014
- Dolichol kinase deficiency (DOLK-CDG) with a purely neurological presentation caused by a novel mutationMolecular Genetics and Metabolism, 2013
- Understanding Human Glycosylation Disorders: Biochemistry Leads the ChargeOnline Journal of Public Health Informatics, 2013
- A zebrafish model of PMM2-CDG reveals altered neurogenesis and a substrate-accumulation mechanism for N-linked glycosylation deficiencyMolecular Biology of the Cell, 2012
- From glycosylation disorders to dolichol biosynthesis defects: a new class of metabolic diseasesJournal of Inherited Metabolic Disease, 2011
- Inherited Clinical Disorders of Lipid MetabolismDiagnosis and Therapy of Tattoo Complications, 2010
- A method and server for predicting damaging missense mutationsNature Methods, 2010
- Hypoglycosylation due to dolichol metabolism defectsBiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2009
- Thematic review series: Skin Lipids. Pathogenesis of permeability barrier abnormalities in the ichthyoses: inherited disorders of lipid metabolismJournal of Lipid Research, 2008
- The congenital disorders of glycosylation: A multifaceted group of syndromesNeuroRX, 2006