Insights Into the Pathological Glycosylation Associated With COG6-CDG
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F25%3A10506115" target="_blank" >RIV/00216208:11110/25:10506115 - isvavai.cz</a>
Alternative codes found
RIV/00064165:_____/25:10506115
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=PypXEeHhNT" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=PypXEeHhNT</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1155/humu/7948771" target="_blank" >10.1155/humu/7948771</a>
Alternative languages
Result language
angličtina
Original language name
Insights Into the Pathological Glycosylation Associated With COG6-CDG
Original language description
Background and Aims: Congenital disorders of glycosylation (CDG) are rare diseases caused by defects in protein glycosylation. We present an infant with multisystemic clinical involvement, diagnosed with COG6-CDG. Methods: Serum and transferrin-linked N-glycans, as well as serum and apolipoprotein CIII–linked O-glycans, were analyzed by MALDI mass spectrometry. Mutation analysis was performed by next-generation sequencing. Functional studies assessed COG6 subunit expression, cooperating subunits, and retrograde transport. GlycoWorks RapiFluor-MS–based N-glycan labeling with HPLC-FLD and ESI-Orbitrap mass spectrometry enabled further comprehensive glycoprofile analysis. Results: Aberrant glycosylation typical of combined N- and O-glycosylation defects was detected. Mutation analysis identified a novel homozygous variant in the COG6 gene: c.906_907delinsA, p.(His302GlnfsTer4), introducing a premature stop codon and producing a truncated protein of only 304 amino acids. The diagnosis of COG6-CDG was confirmed by the complete absence of the COG6 subunit, impairment of two other cooperating subunits, and delayed retrograde transport. Independent glycoprofile analyses by HPLC-FLD and ESI-Orbitrap revealed a set of potential glycobiomarkers of COG6-CDG, including underprocessed N-glycans Hex3-5HexNAc2, Hex3-5HexNAc3, Hex3-4HexNAc4, and Hex4HexNAc3-4NeuAc1. Conclusion: This study describes a novel COG6 variant leading to complete loss of protein function and major glycosylation abnormalities. Multiomics analysis provided deeper insights into the molecular mechanisms of this rare disease and the function of the COG6 gene and demonstrated how the mutation results in significant alterations in the patient′s (glyco)phenotype.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30101 - Human genetics
Result continuities
Project
<a href="/en/project/NU22-07-00474" target="_blank" >NU22-07-00474: Molecular genetic causes and biochemical consequences of Congenital disorders of glycosylation</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Human Mutation
ISSN
1059-7794
e-ISSN
1098-1004
Volume of the periodical
2025
Issue of the periodical within the volume
1
Country of publishing house
US - UNITED STATES
Number of pages
13
Pages from-to
7948771
UT code for WoS article
001626952400001
EID of the result in the Scopus database
2-s2.0-105023540884