Glycerol kinase deficiency: Evidence for complexity in a single gene disorder
Glycerol kinase deficiency: Evidence for complexity in a single gene disorder
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DOI：
10.1007/s004390100545
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发表时间：
2001-07-01
期刊：
影响因子：
5.3
通讯作者：
McCabe, ERB
中科院分区：
文献类型：
--
作者：
Dipple, KM;Zhang, YH;McCabe, ERB
甘油激酶缺乏症(GKD)是Xp21邻近基因综合征的一部分，也可能是孤立的GKD。这种孤立的形式既可以表现为发作性代谢和中枢神经系统(CNS)失代偿的症状，也可以是无症状的高甘油血症和甘油尿症。为了更好地了解分离的GKD的发病机制，我们寻找了GK编码区有点突变的个体，并检测了他们的GK酶活性。我们确定了6个错义突变个体：无症状男性中有4个(N288D、A305V、M428T和Q438R)，有症状个体中有2个(D198G、R405Q)。在淋巴母细胞系或成纤维细胞中测量的GK活性在有症状和无症状的个体中是相似的。将这些个体的错义突变映射到大肠杆菌GK的三维结构中，结果显示，有症状的个体的突变与无症状个体中的突变子集位于同一区域，毗邻活性部位裂隙。我们的结论是，像许多其他疾病一样，GK基因不能预测GKD的表型。我们假设GKD患者的表型是一个受其他独立遗传基因影响的复杂特征。
Glycerol kinase deficiency (GKD) occurs as part of an Xp21 contiguous gene syndrome or as isolated GKD. The isolated form can be either symptomatic with episodic metabolic and central nervous system (CNS) decompensation or asymptomatic with hyperglycerolemia and glyceroluria only. To better understand the pathogenesis of isolated GKD, we sought individuals with point mutations in the GK coding region and measured their GK enzyme activities. We identified six individuals with missense mutations: four (N288D, A305V, M428T, and Q438R) among males who were asymptomatic and two (D198G, R405Q) in individuals who were symptomatic. GK activity measured in lymphoblastoid cell lines or fibroblasts was similar for the symptomatic and the asymptomatic individuals. Mapping of the individuals' missense mutations to the three-dimensional structure of Escherichia coli GK revealed that the symptomatic individuals' mutations are in the same region as a subset of the mutations among the asymptomatic individuals, adjacent to the active-site cleft. We conclude that, like many other disorders, GK genotype does not predict GKD phenotype. We hypothesize that the phenotype of an individual with GKD is a complex trait influenced by additional, independently inherited genes.