Glycogen Storage Disease Type Ia in Argentina. Two novel Glucose-6-phosphatase mutations affecting protein stability

ANGARONI, C.J.,; KREMER R.D,; ARGARAÑA, CE; CAPRA A.E.P.,; AYALA A.N.G,; PEZZA R.J,; PAN C-J.,; CHOU J.Y.,

ACADEMIC PRESS INC ELSEVIER SCIENCE

Año: 2004 vol. 83 p. 276 - 276

lycogen storage disease type Ia (GSD-Ia) is caused by deleterious mutations in the glucose-6-phosphatase gene (G6PC). A molecularstudy 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 bothp.Thr16Arg and p.Tyr209Cys mutations abolished enzymatic activity as well as reduced G6Pase stability