Analysis of N- and O-linked protein glycosylation in children with Prader-Willi syndrome.
A subset of kids with Prader-Willi syndrome carry a new sugar-marker on apoC-III that may help split the syndrome into clearer subgroups.
01Research in Context
What this study did
Scientists looked at blood proteins in kids with Prader-Willi syndrome. They checked two sugar-coating processes: N-linked and O-linked glycosylation. The team wanted to see if these sugars were different from typical kids.
They found normal N-linked sugars in all kids. But a small group showed low sialic acid on one protein, apoC-III. This is a new clue for doctors.
What they found
Most sugar patterns looked typical. Only some kids had the low-sialic form of apoC-III. This marker could help spot a PWS subgroup in the future.
The study did not test treatments. It only mapped a possible lab sign.
How this fits with other research
Dimitropoulos et al. (2019) and Dimitropoulos et al. (2013) show that PWS kids with the maternal UPD genetic type score as low as kids with ASD on social tests. Munce et al. (2010) did not test behavior, so the new marker might one day link to these social risks.
Ogata et al. (2018) found that autism-like behaviors in PWS fade after age 30, while food issues stay strong. The 2010 paper looked only at children, so we do not yet know if the apoC-III marker tracks age or behavior change.
Barone et al. (2016) also saw low sialic acid, but in a teen with a different disorder. Both studies hint that sugar problems can show up in neuro-genetic conditions, though the meaning for each syndrome is still unclear.
Why it matters
You now have a possible lab cue, low-sialic apoC-III, to flag a PWS subgroup. Pair this insight with social screens from Anastasia et al. to guide early social-skills training. Watch for future papers that test if the marker predicts food or behavior severity.
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02At a glance
03Original abstract
BACKGROUND: Current genotype-phenotype correlations in Prader-Willi syndrome (PWS) are struggling to give an explanation of the diversity in phenotype and there is a need to move towards a molecular understanding of PWS. A range of functions related to glycoproteins are involved in the pathophysiology of PWS and it may be that abnormal glycosylation is contributing to the biological phenotype. The objective of this study was to investigate the state of N- and O-linked glycosylation in children with Prader-Willi syndrome. METHODS: Twenty-three children with PWS and 20 non-PWS controls were included in the study. Protein N-linked glycosylation was assessed by analysing serum transferrin through mass spectrometry and protein O-linked through isoelectric focusing (IEF) of serum apolipoprotein C-III (apoC-III), confirmed by mass spectrometry. RESULTS: The results of this analysis indicated that the N-linked glycosylation pathway in PWS is normal. A subgroup of PWS individuals was found to have a hyposialylated pattern of apoC-III isoforms. This was independent of the underlying genetic mechanism and is the first report of an apoC-III IEF abnormality in PWS. CONCLUSIONS: This is the first report of apoC-III hyposialylation in PWS. As this field is in its infancy, additional study is required before these findings may be used in clinical settings.
Journal of intellectual disability research : JIDR, 2010 · doi:10.1111/j.1365-2788.2010.01323.x