Premium
Clinical phenotype correlates to glycoprotein phenotype in a sib pair with CDG‐Ia
Author(s) -
Barone Rita,
Sturiale Luisa,
Sofia Vito,
Ignoto Antonella,
Fiumara Agata,
Sorge Giovanni,
Garozzo Domenico,
Zappia Mario
Publication year - 2008
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.32446
Subject(s) - glycosylation , phenotype , glycoprotein , transferrin , genotype , allele , clinical phenotype , mutation , genetics , biology , medicine , immunology , gene
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. © 2008 Wiley‐Liss, Inc.