The mutation spectrum of the facilitative glucose transporter gene SLC2A2 (GLUT2) in patients with Fanconi-Bickel syndrome
The mutation spectrum of the facilitative glucose transporter gene SLC2A2 (GLUT2) in patients with Fanconi-Bickel syndrome
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DOI：
10.1007/s00439-001-0638-6
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发表时间：
2002-01-01
期刊：
影响因子：
5.3
通讯作者：
Schaub, J
中科院分区：
文献类型：
--
作者：
Santer, R;Groth, S;Schaub, J
我们报告了 49 名临床诊断为 Fanconi-Bickel 综合征 (FBS) 的患者中总共 23 个 SLC2A2 (GLUT2) 基因的新突变。自 1949 年最初报告以来，我们已在全球范围内找到了来自 88 个家庭的 109 个 FBS 病例，其中超过 50% 已进行了分子遗传学分析。在这 49 名患者中，已检测到 33 种不同的 SLC2A2 突变（9 种错义、7 种无义、10 种移码、7 种剪接位点）。因此，我们的结果证实SLC2A2突变是FBS患者的基本缺陷。在既往 FBS 患者中检测到 SLC2A2 突变，这些患者的一些特征性临床特征（肝肾糖原积累、葡萄糖和半乳糖不耐受、空腹低血糖、特征性管状肾病）和治疗效果首次被描述。在具有非典型临床症状的患者中也发现了突变，例如肠道吸收不良、发育迟缓、无肝肿大或肾脏高滤过。大量病例并非由单一流行的 SLC2A2 突变造成。在很大比例 (74%) 的 FBS 患者中，突变是纯合的，因此我们得出结论，SLC2A2 突变在大多数人群中的患病率相对较低。在 SLC2A2 内，甚至在促进葡萄糖转运蛋白基因的同源序列内，均未检测到突变热点。
We report a total of 23 novel mutations of the SLC2A2 (GLUT2) gene in 49 patients with a clinical diagnosis of Fanconi-Bickel syndrome (FBS). Molecular genetic analysis has now been performed in more than 50% of the 109 FBS cases from 88 families that we have been able to locate world-wide since the original report in 1949. In these 49 patients, 33 different SLC2A2 mutations (9 missense, 7 nonsense, 10 frameshift, 7 splice-site) have been detected. Thus, our results confirm that mutations of SLC2A2 are the basic defect in patients with FBS. Mutations of SLC2A2 were detected in historical FBS patients in whom some of the characteristic clinical features (hepatorenal glycogen accumulation, glucose and galactose intolerance, fasting hypoglycemia, a characteristic tubular nephropathy) and the effect of therapy were described for the first time. Mutations were also found in patients with atypical clinical signs such as intestinal malabsorption, failure to thrive, the absence of hepatomegaly, or renal hyperfiltration. No single prevalent SLC2A2 mutation was responsible for a significant number of cases. In a high percentage (74%) of FBS patients, the mutation is homozygous, so we conclude that the prevalence of SLC2A2 mutations is relatively low in most populations. No mutational hot spots within SLC2A2 or even within homologous sequences among the genes for facilitative glucose transporters were detected.