Key features and clinical variability of COG6-CDG

Area of Science:

• Molecular biology
• Genetics
• Biochemistry

Background:

• The conserved oligomeric Golgi (COG) complex is vital for Golgi trafficking and glycosylation enzyme localization.
• Mutations in COG subunits, excluding COG3, are associated with congenital disorders of glycosylation (CDG).
• Previous reports identified limited cases of biallelic COG6 mutations.

Observation:

• This study details 7 new patients with 4 novel COG6 mutations, expanding the known cohort.
• Clinical variability is observed, but core features of COG6-CDG are delineated.
• Key features include liver involvement, microcephaly, developmental disability, recurrent infections, and early lethality.

Findings:

• Specific ectodermal signs like hypohidrosis (leading to hyperthermia) and hyperkeratosis are noted in COG6-CDG patients.
• A genotype-phenotype correlation is established, ranging from mild Shaheen syndrome to severe, lethal CDG.
• Ectodermal changes appear to be a distinguishing feature of COG6-related disorders compared to other COG deficiencies.

Implications:

• These findings enhance the clinical differentiation of COG6-related disorders.
• The study suggests functional distinctions among COG complex subunits.
• Understanding COG6 mutations aids in diagnosing and managing complex glycosylation disorders.