Glycogen storage disease type Ia in Argentina: two novel glucose-6-phosphatase mutations affecting protein stability.
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.
Angaroni
Celia J
CJ
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
de Kremer
Raquel Dodelson
RD
Argaraña
Carlos E
CE
Paschini-Capra
Ana E
AE
Giner-Ayala
Alicia N
AN
Pezza
Roberto J
RJ
Pan
Chi-Jiunn
CJ
Chou
Janice Y
JY
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
D017931:DNA Primers; D010744:Phosphoric Monoester Hydrolases; D005952:Glucose-6-Phosphatase