Glycosylation Type III, Impaired ... (Congenital disorder of glycosylation type IIi) - Gen COG5.

The alteration of glycosylation of type III (CDG III) is an inherited disease that causes neurological problems and other abnormalities. Individuals with CDG III usually show signs and symptoms of the disease during childhood. The pattern and severity of signs and symptoms varies between individuals affected and may include hypotonia, developmental delay, moderate to severe mental retardation, poor coordination and difficulty walking. Some affected people never learn to speak. Other features of CDG III include short stature, microcephaly and characteristic facial features, which may include low - set ears turned back, short neck with low hairline at the back and a prominent nose. Less frequently, affected individuals may have sensorineural hearing loss, impaired vision, neurogenic bladder, liver disease and contractures.

This process is due to mutations in the gene COG5, located on the long arm of chromosome 7 (7q31). This gene encodes a protein called conserved oligomeric complex Golgi 5 (COG5). As the name suggests, COG5 is a component of a group of proteins known as the conserved Golgi (COG) oligomeric complex. A process performed in the Golgi apparatus is glycosylation amending proteins so they can perform a wider variety of functions. The COG complex takes part in the transport of proteins, including enzymes which perform glycosylation within the Golgi apparatus. Specifically, COG is involved in the retrograde transport of proteins through the Golgi apparatus. Retrograde transport is important for the recycling of Golgi proteins and ensures that they are in the correct location on the structure, which is key to proper glycosylation. Proteins are transported in vesicles adhere to the Golgi membrane and release their contents into the Golgi apparatus.

At least 8 mutations in the gene COG5 generating altered glycosylation of type III (CDG III) are known. Associated mutations reduce the amount of protein COG5 or completely eliminated, which interrupts the retrograde transport into the Golgi apparatus. This alteration results in abnormal glycosylation of proteins, which may affect multiple systems in the body, leading to signs and symptoms of CDG III. The severity of the disease is related to the amount of protein remaining in COG5 cells.

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 altered glycosylation of type III (CDG III), by complete PCR amplification of exons COG5 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).