Further evidence that mutations in INS can be a rare cause of Maturity-Onset Diabetes of the Young (MODY).
Further evidence that mutations in INS can be a rare cause of Maturity-Onset Diabetes of the Young (MODY).
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DOI：
10.1186/1471-2350-11-42
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发表时间：
2010-03-12
影响因子：
--
通讯作者：
Hansen T
中科院分区：
文献类型：
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作者：
Boesgaard TW;Pruhova S;Andersson EA;Cinek O;Obermannova B;Lauenborg J;Damm P;Bergholdt R;Pociot F;Pisinger C;Barbetti F;Lebl J;Pedersen O;Hansen T
胰岛素基因（INS）突变最近被描述为永久性新生儿糖尿病（PNDM）的常见原因，也是儿童或成人糖尿病的罕见原因。对116例青年成熟型糖尿病（MODYX）患者（n = 48丹麦人和n = 68捷克人）、83例妊娠期糖尿病（GDM）患者、34例谷氨酸脱羧酶（GAD）筛查阴性的1型糖尿病患者和96例葡萄糖耐量个体进行INS测序。对照组从基于人群的Inter 99研究中随机选择。在一个丹麦MODYX家族中发现了一个新的杂合突变c.17G>A，R6 H，位于前胰岛素原基因（INS）中。先证者在20岁时被诊断为轻度糖尿病，并接受饮食和口服降糖药治疗。另外两名携带INS R6 H的家庭成员分别在51岁和27岁时被诊断为糖尿病和GDM。第四个突变携带者在20岁时具有正常的葡萄糖耐量。两名INS R6 H携带者也进行了两次口服葡萄糖耐量试验（OGTT），间隔5年。他们都有一个约30%的β细胞功能降低测量胰岛素生成指数。在一个捷克MODYX家族中发现了一个先前描述的R46 Q突变，先证者在13岁时被诊断为糖尿病，自发病以来一直接受胰岛素治疗。她的母亲和祖母分别在14岁和35岁时被确诊，并接受口服降糖药和/或胰岛素治疗。INS突变可能是MODY的罕见原因，我们的结论是，INS突变筛查应推荐在MODYX患者。
Insulin gene (INS) mutations have recently been described as a common cause of permanent neonatal diabetes (PNDM) and a rare cause of diabetes diagnosed in childhood or adulthood. INS was sequenced in 116 maturity-onset diabetes of the young (MODYX) patients (n = 48 Danish and n = 68 Czech), 83 patients with gestational diabetes mellitus (GDM), 34 type 1 diabetic patients screened negative for glutamic acid decarboxylase (GAD), and 96 glucose tolerant individuals. The control group was randomly selected from the population-based sampled Inter99 study. One novel heterozygous mutation c.17G>A, R6H, was identified in the pre-proinsulin gene (INS) in a Danish MODYX family. The proband was diagnosed at 20 years of age with mild diabetes and treated with diet and oral hypoglycaemic agent. Two other family members who carried the INS R6H were diagnosed with diabetes when 51 years old and with GDM when 27 years old, respectively. A fourth mutation carrier had normal glucose tolerance when 20 years old. Two carriers of INS R6H were also examined twice with an oral glucose tolerance test (OGTT) with 5 years interval. They both had a ~30% reduction in beta-cell function measured as insulinogenic index. In a Czech MODYX family a previously described R46Q mutation was found. The proband was diagnosed at 13 years of age and had been treated with insulin since onset of diabetes. Her mother and grandmother were diagnosed at 14 and 35 years of age, respectively, and were treated with oral hypoglycaemic agents and/or insulin. Mutations in INS can be a rare cause of MODY and we conclude that screening for mutations in INS should be recommended in MODYX patients.