Key features and clinical variability of COG6-CDG

6533b838fe1ef96bd12a3dfa

RESEARCH PRODUCT

Key features and clinical variability of COG6-CDG

Christian Thiel Peter M. Van Hasselt Ayşegül Tokatlı Philippe Goyens Gert Matthijs ÇIğdem Seher Kasapkara Oliver Bartsch Daisy Rymen Uwe Kornak Uwe Kornak Hubertus C.m.t. Prinsen Hanneke A. Haijes Gülden Gökçay Eva Mildenberger Jaak Jaeken Julia Winter Peter Krawitz Jochen Hecht

subject

Male Microcephaly Glycosylation Adolescent Endocrinology Diabetes and Metabolism Protein subunit Hyperkeratosis Molecular Sequence Data Golgi Apparatus Case Reports Research Support Biochemistry Conserved oligomeric Golgi complex Young Adult Endocrinology Cog Congenital Disorders of Glycosylation Genetics Journal Article Medicine Humans Non-U.S. Gov't Child Molecular Biology Exome sequencing Genetic Association Studies Genetics business.industry Conserved oligomeric Golgi complex Research Support Non-U.S. Gov't High-Throughput Nucleotide Sequencing Infant Congenital disorder of glycosylation medicine.disease Phenotype Adaptor Proteins Vesicular Transport Phenotype COG6 Mutation Microcephaly Female CDG business Congenital disorder of glycosylation

description

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.

year	journal	country	edition	language
2015-11-01

https://dspace.library.uu.nl/handle/1874/332482