Key features and clinical variability of COG6-CDG

Mol Genet Metab. 2015 Nov;116(3):163-70. doi: 10.1016/j.ymgme.2015.07.003. Epub 2015 Jul 29.

Abstract

The conserved oligomeric Golgi (COG) complex consists of eight subunits and plays a crucial role in Golgi trafficking and positioning of glycosylation enzymes. Mutations in all COG subunits, except subunit 3, have been detected in patients with congenital disorders of glycosylation (CDG) of variable severity. So far, 3 families with a total of 10 individuals with biallelic COG6 mutations have been described, showing a broad clinical spectrum. Here we present 7 additional patients with 4 novel COG6 mutations. In spite of clinical variability, we delineate the core features of COG6-CDG i.e. liver involvement (9/10), microcephaly (8/10), developmental disability (8/10), recurrent infections (7/10), early lethality (6/10), and hypohidrosis predisposing for hyperthermia (6/10) and hyperkeratosis (4/10) as ectodermal signs. Regarding all COG6-related disorders a genotype-phenotype correlation can be discerned ranging from deep intronic mutations found in Shaheen syndrome as the mildest form to loss-of-function mutations leading to early lethal CDG phenotypes. A comparison with other COG deficiencies suggests ectodermal changes to be a hallmark of COG6-related disorders. Our findings aid clinical differentiation of this complex group of disorders and imply subtle functional differences between the COG complex subunits.

Keywords: CDG; COG6; Congenital disorder of glycosylation; Conserved oligomeric Golgi complex.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Vesicular Transport / genetics*
  • Adolescent
  • Child
  • Congenital Disorders of Glycosylation / complications
  • Congenital Disorders of Glycosylation / genetics*
  • Congenital Disorders of Glycosylation / physiopathology*
  • Female
  • Genetic Association Studies
  • Glycosylation
  • Golgi Apparatus / genetics*
  • Golgi Apparatus / pathology
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Infant
  • Male
  • Microcephaly / etiology
  • Molecular Sequence Data
  • Mutation
  • Phenotype
  • Young Adult

Substances

  • Adaptor Proteins, Vesicular Transport
  • COG6 protein, human

Associated data

  • RefSeq/NM_001145079