Aberrant sialylation in a patient with a HNF1α variant and liver adenomatosis
Luisa Sturiale,
Marie-Cécile Nassogne,
Angelo Palmigiano,
Angela Messina,
Immacolata Speciale,
Rosangela Artuso,
Gaetano Bertino,
Nicole Revencu,
Xavier Stephénne,
Cristina De Castro,
Gert Matthijs,
Rita Barone,
Jaak Jaeken,
Domenico Garozzo
Affiliations
Luisa Sturiale
CNR, Institute for Polymers, Composites and Biomaterials, IPCB, 95126 Catania, Italy
Marie-Cécile Nassogne
Pediatric Neurology Unit, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, 1200 Brussels, Belgium
Angelo Palmigiano
CNR, Institute for Polymers, Composites and Biomaterials, IPCB, 95126 Catania, Italy
Angela Messina
CNR, Institute for Polymers, Composites and Biomaterials, IPCB, 95126 Catania, Italy
Immacolata Speciale
Department of Chemical Sciences, University of Naples Federico II, 80100 Naples, Italy; Department of Agricultural Sciences, University of Naples Federico II, 80055 Portici, Italy
Rosangela Artuso
Medical Genetics Unit, Meyer Children's University Hospital, 50100 Florence, Italy
Gaetano Bertino
Hepatology Unit, A.O.U. Policlinico-Vittorio Emanuele, Department of Clinical and Experimental Medicine, University of Catania, 95100 Catania, Italy
Nicole Revencu
Center for Human Genetics, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, 1200 Brussels, Belgium
Xavier Stephénne
Service de Gastro-Entérologie et Hépatologie Pédiatrique, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, 1200 Brussels, Belgium
Cristina De Castro
Department of Agricultural Sciences, University of Naples Federico II, 80055 Portici, Italy
Gert Matthijs
Department of Human Genetics, Laboratory for Molecular Diagnosis, KU Leuven, 3000 Leuven, Belgium
Rita Barone
CNR, Institute for Polymers, Composites and Biomaterials, IPCB, 95126 Catania, Italy; Child Neurology and Psychiatry, Department of Clinical and Experimental Medicine, University of Catania, 95100 Catania, Italy
Jaak Jaeken
Center for Metabolic Diseases, UZ and KU Leuven, 3000 Leuven, Belgium
Domenico Garozzo
CNR, Institute for Polymers, Composites and Biomaterials, IPCB, 95126 Catania, Italy; Corresponding author
Summary: 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.
