COG5-congenital disorder of glycosylation (COG5-CDG, formerly known as congenital disorder of glycosylation type IIi) is an inherited condition that causes neurological problems and other abnormalities. The pattern and severity of this disorder's signs and symptoms vary among affected individuals.

Individuals with COG5-CDG typically develop signs and symptoms of the condition during infancy. These individuals often have weak muscle tone (hypotonia) and delayed development. Other neurological features include moderate to severe intellectual disability, poor coordination, and difficulty walking. Some affected individuals never learn to speak. Other features of COG5-CDG include short stature, an unusually small head size (microcephaly), and distinctive facial features, which can include ears that are set low and rotated backward, a short neck with a low hairline in the back, and a prominent nose. Less commonly, affected individuals can have hearing loss caused by changes in the inner ear (sensorineural hearing loss), vision impairment, damage to the nerves that control bladder function (a condition called neurogenic bladder), liver disease, and joint deformities (contractures).

COG5-CDG is caused by mutations in the COG5 gene, which provides instructions for making one piece of a group of proteins known as the conserved oligomeric Golgi (COG) complex. This complex functions in the Golgi apparatus, which is a cellular structure in which newly produced proteins are modified. One process that occurs in the Golgi apparatus is glycosylation, by which sugar molecules (oligosaccharides) are attached to proteins and fats. Glycosylation modifies proteins so they can perform a wider variety of functions.

The COG complex takes part in the transport of proteins, including those that perform glycosylation, in the Golgi apparatus. COG5 gene mutations reduce the amount of COG5 protein or eliminate it completely, which disrupts protein transport. This disruption results in abnormal protein glycosylation, which can affect numerous body systems, leading to the signs and symptoms of COG5-CDG. The severity of COG5-CDG is related to the amount of COG5 protein that remains in cells.

Normal Function

The COG5 gene provides instructions for making a protein called component of oligomeric Golgi complex 5 (COG5). As its name suggests, COG5 is one piece of a group of proteins known as the conserved oligomeric Golgi (COG) complex. This complex functions in the Golgi apparatus, which is a cell structure in which newly produced proteins are modified. One process that occurs in the Golgi apparatus is glycosylation, by which sugar molecules (oligosaccharides) are attached to proteins and fats. Glycosylation modifies proteins so they can perform a wider variety of functions.

The COG complex takes part in the transport of proteins, including the enzymes that perform glycosylation, within the Golgi apparatus. COG is specifically involved in retrograde transport, which moves proteins backward through the Golgi apparatus. Retrograde transport is important for recycling Golgi proteins and ensuring that they are in the correct location in the structure, which is key to proper glycosylation. The proteins are transported in sac-like structures called vesicles that attach to the Golgi membrane and release the contents into the Golgi apparatus. The COG complex controls the attachment (tethering) of the vesicles to the Golgi membrane.

Health Conditions Related to Genetic Changes

COG5-congenital disorder of glycosylation

At least eight mutations in the COG5 gene are known to cause COG5-congenital disorder of glycosylation (COG5-CDG). This condition often leads to developmental delay and intellectual disability and causes other abnormalities. Mutations in the COG5 gene reduce the amount of COG5 protein or eliminate it completely, which disrupts retrograde transport in the Golgi apparatus. This disruption results in abnormal protein glycosylation, which can affect multiple body systems, leading to the signs and symptoms of COG5-CDG. The severity of the condition is related to the amount of COG5 protein that remains in cells.

Other Names for This Gene

• 13S golgi transport complex 1 90 kDa subunit
• CDG2I
• COG complex subunit 5
• conserved oligomeric Golgi complex protein 5
• conserved oligomeric Golgi complex subunit 5
• GOLTC1
• GTC90

Genomic Location

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

COG5-CDG is a very rare disorder; fewer than 10 cases have been described in the medical literature.