Glycogen storage disease type Ia in Argentina:: two novel glucose-6-phosphatase mutations affecting protein stability
Glycogen storage disease type Ia in Argentina:: two novel glucose-6-phosphatase mutations affecting protein stability
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DOI：
10.1016/j.ymgme.2004.06.010
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发表时间：
2004-11-01
影响因子：
3.8
通讯作者：
Chou, JY
中科院分区：
文献类型：
--
作者：
Angaroni, CJ;de Kremer, RD;Chou, JY
Ia 型糖原贮积病 (GSD-Ia) 是由葡萄糖 6 磷酸酶基因 (G6PC) 的有害突变引起的。对来自 8 个不相关家庭的 11 名阿根廷患者进行了对该基因的分子研究。已鉴定出四种错义突变（p.Gln54Pro、p.Arg83Cys、p.Thr16Arg 和 p.Tyr209Cys）和一种缺失突变（c.79delC）。本研究发现了两个新突变，即位于氨基末端结构域内的 p.Thr16Arg (c.47C>G) 和位于第六跨膜螺旋内的 p.Tyr209Cys (c.626A>G)。定点诱变和瞬时表达测定表明，p.Thr16Arg 和 p.Tyr209Cys 突变都会消除酶活性并降低 G6Pase 稳定性。 (C) 2004 Elsevier Inc. 保留所有权利。
Glycogen storage disease type la (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. (C) 2004 Elsevier Inc. All rights reserved.