Key features and clinical variability of COG6-CDG.


Rymen D., Winter J., Van Hasselt P. M. , Jaeken J., Kasapkara C., Gokcay G. F. , ...Daha Fazla

Molecular genetics and metabolism, cilt.116, ss.163-70, 2015 (SCI Expanded İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 116 Konu: 3
  • Basım Tarihi: 2015
  • Doi Numarası: 10.1016/j.ymgme.2015.07.003
  • Dergi Adı: Molecular genetics and metabolism
  • Sayfa Sayıları: ss.163-70

Özet

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 COG 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. (C) 2015 Published by Elsevier Inc.