The Swedish COG6-CDG experience and a comprehensive literature review.
Zhi-Jie XiaBobby G NgElizabeth JennionsMaria BlomqvistAnneli Sandqvist WiklundCarola Hedberg-OldforsCarlos Rodriguez GonzalezHudson H FreezeSofia YgbergErik A EklundPublished in: JIMD reports (2022)
Here, we present the first two Swedish cases of Conserved Oligomeric Golgi complex subunit 6-congenital disorders of glycosylation (COG6-CDG). Their clinical symptoms include intellectual disability, Attention Deficit/Hyperactivity Disorder (ADHD), delayed brain myelinization, progressive microcephaly, joint laxity, hyperkeratosis, frequent infections, and enamel hypoplasia. In one family, compound heterozygous variants in COG6 were identified, where one (c.785A>G; p.Tyr262Cys) has previously been described in patients of Moroccan descent, whereas the other (c.238G>A; p.Glu80Lys) is undescribed. On the other hand, a previously undescribed homozygous duplication (c.1793_1795dup) was deemed the cause of the disease. To confirm the pathogenicity of the variants, we treated patient and control fibroblasts with the ER-Golgi transport inhibitor Brefeldin-A and show that patient cells manifest a significantly slower anterograde and retrograde ER-Golgi transport.
Keyphrases
- attention deficit hyperactivity disorder
- intellectual disability
- autism spectrum disorder
- endoplasmic reticulum
- case report
- end stage renal disease
- newly diagnosed
- copy number
- working memory
- induced apoptosis
- chronic kidney disease
- multiple sclerosis
- zika virus
- estrogen receptor
- cell cycle arrest
- prognostic factors
- peritoneal dialysis
- white matter
- gene expression
- resting state
- signaling pathway
- sleep quality
- depressive symptoms
- dna methylation
- cell proliferation
- patient reported
- subarachnoid hemorrhage
- brain injury
- cerebral ischemia