COG1 – Congenital Disorders of Glycosylation

The association between COG1 and congenital disorders of glycosylation (MONDO_0015286) is supported by clinical case reports and multi‐patient studies. Five probands have been reported with pathogenic variants in COG1, demonstrating an autosomal recessive pattern (PMID:33960418).

Genetic evidence is highlighted by the identification of a homozygous frameshift variant, c.2665dup (p.Arg889ProfsTer12), in a patient presenting with hepatitis and other features of CDG. This variant disrupts protein function in a manner consistent with disease pathology, and its detection in the proband supports a pathogenic role (PMID:33960418).

While detailed familial segregation data are limited, the observed variant has been identified in an affected individual with a phenotype that aligns with a defect in glycosylation. The clinical findings across the reported cases underscore its relevance in the diagnostic setting.

Functional studies further validate this association. Research indicates that disruption of the COG complex, particularly through impaired interaction between COG1 and COG8, leads to defective glycosylation. These mechanistic insights, derived from experimental models, reinforce the impact of COG1 deficiency on normal Golgi function (PMID:17220172).

The integration of these genetic and functional data establishes a Moderate level of evidence for the association between COG1 and congenital disorders of glycosylation. Although additional cases would further solidify this link, current evidence is sufficient to guide diagnostic decisions, support commercial assay development, and inform future publications.

Key take‑home: Comprehensive evaluation of COG1 variants is clinically valuable in the diagnosis of congenital disorders of glycosylation, offering essential insights for patient management and genetic counseling.

References

• Clinical genetics • 2021 • COG1‑congenital disorders of glycosylation: Milder presentation and review. PMID:33960418
• Human molecular genetics • 2007 • A new inborn error of glycosylation due to a Cog8 deficiency reveals a critical role for the Cog1-Cog8 interaction in COG complex formation. PMID:17220172

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