: Glycosylation is a fundamental post-translational modification of proteins that boosts their structural diversity providing subtle and specialized biological properties and functions. All those genetic diseases due to a defective glycan biosynthesis and attachment to the nascent glycoproteins fall within the wide area of congenital disorders of glycosylation (CDG), mostly causing multisystem involvement. In the present paper, we detailed the unique serum N-glycosylation of a CDG-candidate patient with an unexplained neurological phenotype and liver adenomatosis harboring a recurrent pathogenic HNF1α variant. Serum transferrin isoelectric focusing showed a surprising N-glycosylation pattern consisting on hyposialylation, as well as remarkable hypersialylation. Mass spectrometry-based glycomic analyses of individual serum glycoproteins enabled to unveil hypersialylated complex N-glycans comprising up to two sialic acids per antenna. Further advanced MS analysis showed the additional sialic acid is bonded through an α2-6 linkage to the peripheral N-acetylglucosamine residue.

Aberrant sialylation in a patient with a HNF1α variant and liver adenomatosis / Sturiale, Luisa; Nassogne, Marie-Cécile; Palmigiano, Angelo; Messina, Angela; Speciale, Immacolata; Artuso, Rosangela; Bertino, Gaetano; Revencu, Nicole; Stephénne, Xavier; De Castro, Cristina; Matthijs, Gert; Barone, Rita; Jaeken, Jaak; Garozzo, Domenico. - In: ISCIENCE. - ISSN 2589-0042. - 24:4(2021), p. 102323. [10.1016/j.isci.2021.102323]

Aberrant sialylation in a patient with a HNF1α variant and liver adenomatosis

Speciale, Immacolata;De Castro, Cristina;
2021

Abstract

: Glycosylation is a fundamental post-translational modification of proteins that boosts their structural diversity providing subtle and specialized biological properties and functions. All those genetic diseases due to a defective glycan biosynthesis and attachment to the nascent glycoproteins fall within the wide area of congenital disorders of glycosylation (CDG), mostly causing multisystem involvement. In the present paper, we detailed the unique serum N-glycosylation of a CDG-candidate patient with an unexplained neurological phenotype and liver adenomatosis harboring a recurrent pathogenic HNF1α variant. Serum transferrin isoelectric focusing showed a surprising N-glycosylation pattern consisting on hyposialylation, as well as remarkable hypersialylation. Mass spectrometry-based glycomic analyses of individual serum glycoproteins enabled to unveil hypersialylated complex N-glycans comprising up to two sialic acids per antenna. Further advanced MS analysis showed the additional sialic acid is bonded through an α2-6 linkage to the peripheral N-acetylglucosamine residue.
2021
Aberrant sialylation in a patient with a HNF1α variant and liver adenomatosis / Sturiale, Luisa; Nassogne, Marie-Cécile; Palmigiano, Angelo; Messina, Angela; Speciale, Immacolata; Artuso, Rosangela; Bertino, Gaetano; Revencu, Nicole; Stephénne, Xavier; De Castro, Cristina; Matthijs, Gert; Barone, Rita; Jaeken, Jaak; Garozzo, Domenico. - In: ISCIENCE. - ISSN 2589-0042. - 24:4(2021), p. 102323. [10.1016/j.isci.2021.102323]
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/865762
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 6
  • ???jsp.display-item.citation.isi??? 6
social impact