SLC2A2 mutations can cause neonatal diabetes, suggesting GLUT2 may have a role in human insulin secretion
SLC2A2 mutations can cause neonatal diabetes, suggesting GLUT2 may have a role in human insulin secretion
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DOI：
10.1007/s00125-012-2595-0
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发表时间：
2012-09-01
期刊：
影响因子：
8.2
通讯作者：
Hattersley, A. T.
中科院分区：
文献类型：
--
作者：
Sansbury, F. H.;Flanagan, S. E.;Hattersley, A. T.
基因SLC 2A 2编码GLUT 2，其主要存在于胰腺、肝脏、肾脏和肠中。在小鼠中，GLUT 2是进入胰腺β细胞的主要葡萄糖转运蛋白，双等位基因Slc 2a 2失活导致致命的新生儿糖尿病。GLUT 2在人类β细胞中的作用是有争议的，双等位基因SLC 2A 2突变导致Fanconi-Bickel综合征（FBS），糖尿病很少报道。我们通过检测SLC 2A 2突变是否会在FBS临床特征出现之前与新生儿糖尿病一起出现来研究GLUT 2在新生儿期的潜在作用。（TNDM; n = 25）或永久性新生儿糖尿病（PNDM; n = 79），我们使用测序和纯合性作图的联合方法排除了新生儿糖尿病的常见遗传原因。在104名患者中，发现5例（5%）具有纯合SLC 2A 2突变，包括4个新突变（S203 R、M376 R、c.963+1G > A、F114 LfsX 16）。5例SLC 2A 2突变患者中有4例表现为孤立性糖尿病，后来发展为FBS特征。5例患者中有4例患有TNDM（我们的TNDM队列中有16%病因不明）。一名PNDM患者在28个月时仍在使用胰岛素。SLC 2A 2突变是新生儿糖尿病的常染色体隐性遗传原因，在排除常见原因后，即使没有FBS的特征，也应在近亲家庭或TNDM患者中考虑。具有纯合SLC 2A 2突变的患者可能患有新生儿糖尿病的发现支持了GLUT 2在人类β细胞中的作用。
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.