Here we show that while POFUT2 is required for secretion of all targets tested, B3GLCT only affects the secretion of a subset, consistent with the observation that B3GLCT mutant phenotypes in PPS patients are less severe than embryonic lethal phenotypes of Pofut2-null mice.
We also demonstrate that mutations in RIPK4 can cause features with a range of severity along the PPS-BPS spectrum and that mutations in IKKA can cause a range of features along the BPS-Cocoon spectrum.
In conclusion, we showed that in mice RIPK4 is implicated in cortical actin organization and in E-cadherin localization or function, which can explain the characteristic epithelial fusions observed in PPSs.
Pain VAS score and 6MWT improved significantly in the IVIG-treated patients when compared with baseline Relative expression of TNF and IFN-γ in both PBMCs and CSF from PPS patients were increased compared to OND subjects at baseline (p < 0.05).
Direct arginine vasopressin (AVP) assessment during water deprivation test (WDT) remains the gold standard in PPS differential diagnosis despite well characterised limitations in this procedure.
Copeptin evaluation holds promises as a diagnostic tool in paediatric PPS; its interpretation might be useful to promptly distinguish NDI, even avoiding the WDT need.
B3GLCT was shown to participate in a non-canonical ER quality control mechanism; however, the exact molecular processes affected in PPS are not well understood.
We also report the absence of B3GALTL mutations in 55 cases of PPS-like phenotypes or isolated Peters anomaly, further establishing the strong association of B3GALTL mutations with classic PPS only.
Mutations of F-box only protein 7 (FBXO7) gene are associated with a severe form of autosomal recessive juvenile Parkinson's disease (PD) (PARK15) with clinical features of Parkinsonian-Pyramidal syndrome (PPS).
This pathway has been implicated in various neurodegenerative diseases, and identification of FBXO7 as the causative gene of PPS is expected to shed new light on its role.
These are similar to Bartsocas-Papas syndrome and popliteal pterygium syndrome (PPS) in humans, for which causative mutations have been documented in the RIPK4 and IRF6 (interferon regulatory factor 6) gene, respectively.
We also demonstrate that mutations in RIPK4 can cause features with a range of severity along the PPS-BPS spectrum and that mutations in IKKA can cause a range of features along the BPS-Cocoon spectrum.