Takahashi K, Akanuma J, Matsubara Y, Fujii K, Kure S, Suzuki Y, Wataya K, Sakamoto O, Aoki Y, Ogasawara M, Ohura T, Miyabayashi S, Narisawa K
Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Japan.
Am J Med Genet. 2000 May 15;92(2):90-4.
Glycogen storage disease type Ia (GSD-Ia) is an autosomal recessive disorder of glycogen metabolism caused by glucose-6-phosphatase (G6Pase) deficiency. It is characterized by short stature, hepatomegaly, hypoglycemia, hyperuricemia, and lactic acidemia. Various mutations have been reported in the G6Pase gene (G6PC). However, in Japanese patients, a g727t substitution was found to be the major cause of GSD-Ia, accounting for 20 of 22 mutant alleles [Kajihara et al., 1995], and no other mutations have been found in this population. We analyzed four Japanese GSD-Ia patients and identified three other mutations in addition to the g727t. They included two missense mutations (R83H and P257L) and one nonsense mutation (R170X). Each of the three mutations exhibited markedly decreased G6Pase activity when expressed in COS7 cells. A patient homozygous for R170X showed multiple episodes of profound hypoglycemia associated with convulsions, while P257L was associated with a mild clinical phenotype. The presence of R170X in three unrelated families may implicate that it is another important mutation in the etiology of GSD-Ia in Japanese patients. Thus, the detection of non-g727t mutations is also important in establishing the DNA-based diagnosis of GSD-Ia in this population.
Ia型糖原贮积病（GSD-Ia）是一种常染色体隐性遗传性糖原代谢紊乱疾病，由葡萄糖-6-磷酸酶（G6Pase）缺乏引起。其特征为身材矮小、肝肿大、低血糖、高尿酸血症和乳酸性血症。G6Pase基因（G6PC）已报道有多种突变。然而，在日本患者中，发现g727t替换是GSD-Ia的主要病因，在22个突变等位基因中有20个为此突变[Kajihara等人，1995年]，且在该人群中未发现其他突变。我们分析了4名日本GSD-Ia患者，除g727t外还鉴定出另外3种突变。它们包括2个错义突变（R83H和P257L）和1个无义突变（R170X）。这3种突变在COS7细胞中表达时均表现出G6Pase活性显著降低。R170X纯合子患者出现多次严重低血糖并伴有惊厥，而P257L与轻度临床表型相关。在3个无亲缘关系的家族中存在R170X，这可能意味着它是日本患者GSD-Ia病因中的另一个重要突变。因此，检测非g727t突变对于在该人群中建立基于DNA的GSD-Ia诊断也很重要。
