title: Clinical phenotype correlates to glycoprotein phenotype in a sib pair with CDG-Ia.
abstract: Congenital disorder of glycosylation (CDG) type Ia (PMM2 mutations) is the most common genetic disorder of protein N-glycosylation. The wide clinical spectrum with mild to severe impairment of neurological function and extensive allelic heterogeneity hamper phenotype-genotype comparison. We report on two male adult siblings with the PMM2 mutations c. 385G > A (p.V129M) and c. 422G > A (p.R141H) and partially different clinical phenotype. Patient 2 has a more severe degree of neurological and systemic involvement and a more pronounced decrease in levels of serum glycoproteins. MALDI-TOF mass spectrometry of serum transferrin and alpha-1-antitrypsin shows more pronounced glycosylation defects in the more severely affected patient. Glycoproteomic analysis may reveal differences in CDG-Ia patients with different disease severity and might endorse clinical characterization of CDG-Ia patients.
authors.affiliation: Institute of Chemistry and Technology of Polymers, CNR, Catania, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Barone
authors.forename: Luisa
authors.initials: L
authors.lastname: Sturiale
authors.forename: Vito
authors.initials: V
authors.lastname: Sofia
authors.forename: Antonella
authors.initials: A
authors.lastname: Ignoto
authors.forename: Agata
authors.initials: A
authors.lastname: Fiumara
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sorge
authors.forename: Domenico
authors.initials: D
authors.lastname: Garozzo
authors.forename: Mario
authors.initials: M
authors.lastname: Zappia
mesh_terms: D000328:Adult; D018981:Congenital Disorders of Glycosylation / Q000201:enzymology / Q000235:genetics*; D006023:Glycoproteins / Q000097:blood / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D017875:Phosphotransferases (Phosphomutases) / Q000235:genetics*; D011134:Polysaccharides / Q000097:blood / Q000378:metabolism; D035781:Siblings; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014168:Transferrin / Q000378:metabolism; D000515:alpha 1-Antitrypsin / Q000097:blood / Q000378:metabolism
chemical_list: D006023:Glycoproteins; D011134:Polysaccharides; D014168:Transferrin; D000515:alpha 1-Antitrypsin; D017875:Phosphotransferases (Phosphomutases); C519582:phosphomannomutase 2, human