Molecular genetics of glycogen-storage disease type 1a in Chinese patients of Taiwan.
Molecular genetics of glycogen-storage disease type 1a in Chinese patients of Taiwan.
复制标题
台湾中国患者 1a 型糖原贮积病的分子遗传学。
DOI：
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发表时间：
2001
影响因子：
3.8
通讯作者：
Tian
中科院分区：
文献类型：
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作者：
Lee;W. Hwu;Pu Dai;Tian
应用聚合酶链式反应/限制性片段长度多态性、时间温度梯度凝胶电泳法和DNA直接测序法，对台湾地区1a型糖原贮积症患者的葡萄糖6-磷酸酶(G6Pase)基因突变谱进行了研究。除了RFLP检测到的两个最常见的突变727G->；T(44.4%)和R83H(36.1%)外，还发现了另外五个突变：341delG、933insAA、Q104X、I341N和H119L。移码突变(341delG和933insAA)和产生截短蛋白的无义突变(Q104X)被预测会导致疾病。错义突变I341N发生在ER结合酶的最后一个跨膜区，保留了少量约10%的残余活性。除了R83H，这些突变只在亚洲人中被描述过。然而，H119L特别令人感兴趣，因为磷酸水解酶的催化组氨酸具有重要作用。这种氨基酸被认为参与了催化过程中磷酸-酶中间体的形成。727G-->；T和H119L突变复合杂合子的患者在她的肝脏活检中基本上没有G6Pase活性。这与H119L在催化中的重要性是一致的。
The mutation spectrum of the glucose 6-phosphatase (G6Pase) gene in Chinese patients with type 1a glycogen-storage disease of Taiwan was studied by PCR/RFLP, temporal temperature gradient gel electrophoresis, and direct DNA sequencing methods. In addition to the two most prevalent mutations, 727G --> T (44.4%) and R83H (36.1%), that were detected by RFLP analysis, five other mutations, 341delG, 933insAA, Q104X, I341N, and H119L were identified. The frameshift mutations (341delG and 933insAA) and the nonsense mutation (Q104X) that produce truncated proteins are predicted to be disease-causing. The missense mutation, I341N, occurring in the last transmembrane domain of the ER-bound enzyme, retains a small amount of residual activity of approximately 10%. Except for R83H, the mutations have been described only in Asians. H119L, however, is of particular interest because of the essential role of the catalytic histidine of phosphohydrolase. This amino acid is believed to be involved in the formation of the phosphoryl-enzyme intermediate during catalysis. The patient who was compound heterozygous for 727G --> T and H119L mutations had essentially no G6Pase activity in her liver biopsy. This observation is consistent with the importance of H119L in catalysis.