title: Glycogen storage disease type Ia in Argentina: two novel glucose-6-phosphatase mutations affecting protein stability.
abstract: Glycogen storage disease type Ia (GSD-Ia) is caused by deleterious mutations in the glucose-6-phosphatase gene (G6PC). A molecular study of this gene was carried out in 11 Argentinean patients from 8 unrelated families. Four missense (p.Gln54Pro, p.Arg83Cys, p.Thr16Arg, and p.Tyr209Cys) and one deletion (c.79delC) mutations have been identified. Two novel mutations, p.Thr16Arg (c.47C>G) located within the amino-terminal domain and p.Tyr209Cys (c.626A>G) situated in the sixth transmembrane helix, were uncovered in this study. Site-directed mutagenesis and transient expression assays demonstrated that both p.Thr16Arg and p.Tyr209Cys mutations abolished enzymatic activity as well as reduced G6Pase stability.
authors.affiliation: Centro de Estudio de las Metabolopatías Congénitas, CEMECO, Cátedra de Clínica Pediátrica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Hospital de Niños de la Santísima Trinidad, Córdoba, Argentina. celiangaroni@hotmail.com
authors.forename: Celia J
authors.initials: CJ
authors.lastname: Angaroni
authors.forename: Raquel Dodelson
authors.initials: RD
authors.lastname: de Kremer
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Argaraña
authors.forename: Ana E
authors.initials: AE
authors.lastname: Paschini-Capra
authors.forename: Alicia N
authors.initials: AN
authors.lastname: Giner-Ayala
authors.forename: Roberto J
authors.initials: RJ
authors.lastname: Pezza
authors.forename: Chi-Jiunn
authors.initials: CJ
authors.lastname: Pan
authors.forename: Janice Y
authors.initials: JY
authors.lastname: Chou
mesh_terms: D000818:Animals; D001118:Argentina; D015153:Blotting, Western; D019556:COS Cells; D006224:Cricetinae; D003412:Cricetulus; D004252:DNA Mutational Analysis; D017931:DNA Primers; D005260:Female; D017353:Gene Deletion; D015870:Gene Expression; D005952:Glucose-6-Phosphatase / Q000235:genetics* / Q000378:metabolism; D005953:Glycogen Storage Disease Type I / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D016297:Mutagenesis, Site-Directed; D020125:Mutation, Missense / Q000235:genetics*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism
chemical_list: D017931:DNA Primers; D010744:Phosphoric Monoester Hydrolases; D005952:Glucose-6-Phosphatase