Peninsula College of Medicine and Dentistry, University of Exeter, Peninsula Medical School Building, Barrack Road, Exeter, Devon EX2 5DW, UK.
Diabetologia. 2012 Sep;55(9):2381-5. doi: 10.1007/s00125-012-2595-0. Epub 2012 Jun 2.
The gene SLC2A2 encodes GLUT2, which is found predominantly in pancreas, liver, kidney and intestine. In mice, GLUT2 is the major glucose transporter into pancreatic beta cells, and biallelic Slc2a2 inactivation causes lethal neonatal diabetes. The role of GLUT2 in human beta cells is controversial, and biallelic SLC2A2 mutations cause Fanconi-Bickel syndrome (FBS), with diabetes rarely reported. We investigated the potential role of GLUT2 in the neonatal period by testing whether SLC2A2 mutations can present with neonatal diabetes before the clinical features of FBS appear.
We studied SLC2A2 in patients with transient neonatal diabetes mellitus (TNDM; n = 25) or permanent neonatal diabetes mellitus (PNDM; n = 79) in whom we had excluded the common genetic causes of neonatal diabetes, using a combined approach of sequencing and homozygosity mapping.
Of 104 patients, five (5%) were found to have homozygous SLC2A2 mutations, including four novel mutations (S203R, M376R, c.963+1G>A, F114LfsX16). Four out of five patients with SLC2A2 mutations presented with isolated diabetes and later developed features of FBS. Four out of five patients had TNDM (16% of our TNDM cohort of unknown aetiology). One patient with PNDM remains on insulin at 28 months.
SLC2A2 mutations are an autosomal recessive cause of neonatal diabetes that should be considered in consanguineous families or those with TNDM, after excluding common causes, even in the absence of features of FBS. The finding that patients with homozygous SLC2A2 mutations can have neonatal diabetes supports a role for GLUT2 in the human beta cell.
SLC2A2 基因编码 GLUT2，主要存在于胰腺、肝脏、肾脏和肠道中。在小鼠中，GLUT2 是进入胰腺β细胞的主要葡萄糖转运体，而 SLC2A2 的双等位基因失活会导致致命性新生儿糖尿病。GLUT2 在人类β细胞中的作用存在争议，而 SLC2A2 的双等位基因突变会导致 Fanconi-Bickel 综合征（FBS），但很少有糖尿病报道。我们通过测试 SLC2A2 突变是否会在 FBS 临床特征出现之前导致新生儿糖尿病，来研究 GLUT2 在新生儿期的潜在作用。
我们使用测序和纯合子作图的联合方法，研究了排除了新生儿糖尿病常见遗传原因的 25 例短暂性新生儿糖尿病（TNDM）和 79 例永久性新生儿糖尿病（PNDM）患者的 SLC2A2。
在 104 名患者中，发现 5 名（5%）患者存在 SLC2A2 纯合突变，包括 4 种新突变（S203R、M376R、c.963+1G>A、F114LfsX16）。SLC2A2 突变的 5 名患者中有 4 名仅表现为糖尿病，随后出现 FBS 的特征。SLC2A2 突变的 5 名患者中有 4 名（我们未知病因的 TNDM 队列的 16%）为 TNDM。1 名 PNDM 患者在 28 个月时仍依赖胰岛素。
SLC2A2 突变是一种常染色体隐性遗传原因导致的新生儿糖尿病，在排除常见原因后，尤其是在没有 FBS 特征的情况下，应考虑在近亲家庭或 TNDM 患者中考虑 SLC2A2 突变。发现纯合 SLC2A2 突变的患者可能患有新生儿糖尿病，这支持 GLUT2 在人类β细胞中的作用。
