DOLK, altered glycosylation ... (DOLK-CDG) (DOLK-congenital disorder of glycosylation) - Gen DOLK.
Congenital impaired DOLK glycosylation (CDG-DOLK, formerly known as congenital disorder of glycosylation type Im) is a hereditary disease that affects the heart, but may also affect other body systems.
The pattern and severity of signs and symptoms of this process vary among affected individuals. These signs and symptoms usually occur in infancy or early childhood, and include dilated cardiomyopathy, recurrent seizures, developmental delay, hypotonia and ichthyosis. Less frequently, affected individuals may have distinctive facial features, kidney disease, hormonal disorders or eye problems. Individuals with DOLK-CDG tend not normally survive to adulthood, due to complications related to dilated cardiomyopathy, and some do not survive beyond infancy.
This process is due to mutations in the gene DOLK, located on the long arm of chromosome 9 (9q34.11). This gene encodes the enzyme dolichol kinase, which facilitates the final step of production dolichol phosphate, a critical compound for glycosylation. Dolichol kinase is located in the endoplasmic reticulum, involved in the processing and transport of proteins. This enzyme adds a phosphate group to produce compound dolichol dolichol phosphate. During glycosylation, dolichol phosphate sugars are added to form the oligosaccharide chain. Once the chain is formed, the dolichol phosphate transports the oligosaccharide to the protein to be glycosylated and binds to a specific site on the protein. Dolichol phosphate is also required for GPI anchor formation.
They have identified at least six mutations in the gene DOLK in people with CDG-DOLK. These genetic alterations in amino acid change dolichol kinase enzyme, which results in an enzyme with reduced or absent activity. Consequently, dolichol phosphate and glycosylation does not occur can not be performed. It has been shown that a protein known to stabilize the heart muscle fibers, called alpha dystroglycan, reduced glycosylation in people with DOLK-CDG. Deterioration of alpha dystroglycan glycosylation alters their normal function, which damages the heart muscle fibers. Eventually, the fibers are weakened and break, leading to dilated cardiomyopathy. Other signs and symptoms of CDG-DOLK are probably due to abnormal glycosylation of additional proteins in other organs and tissues.
This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with congenital disorder of DOLK (CDG-DOLK) glycosylation, by complete PCR amplification of exons DOLK gene, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).