A case of novel de novo paired box gene 6 (PAX6) mutation with early-onset diabetes mellitus and aniridia
A case of novel de novo paired box gene 6 (PAX6) mutation with early-onset diabetes mellitus and aniridia
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DOI：
10.1111/j.1464-5491.2005.01469.x
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发表时间：
2005-05-01
影响因子：
3.5
通讯作者：
Nanjo, K
中科院分区：
文献类型：
--
作者：
Nishi, M;Sasahara, M;Nanjo, K
背景 配对盒基因 6 (PAX6) 是一种参与眼睛发育的转录因子。 PAX6 突变会导致先天性眼睛异常，例如无虹膜。 PAX6 还参与内分泌胰腺的发育，据报道是无虹膜和葡萄糖耐受不良的常见遗传因素，尽管后者通常较轻微。在此，我们描述一例 PAX6 突变伴早发性糖尿病的病例。 病例报告 一名 27 岁女性被转诊至我们诊所。她15岁时被诊断患有糖尿病，谷氨酸脱羧酶（GAD）抗体呈阴性。 24 岁时开始接受胰岛素治疗。由于她患有无虹膜症，因此对 PAX6 基因突变进行了研究，并鉴定出杂合 2 bp 缺失 (c.402del2)。她的父母没有虹膜和 PAX6 突变。杂合 PAX6 突变可能导致葡萄糖不耐受。然而，尚未报道早发性糖尿病病例。她的父母没有糖尿病，但他们的胰岛素生成指数较低（分别为0.25和0.3）。我们认为她的早发性糖尿病部分是由于 PAX6 突变造成的，部分是因为从她父母那里继承了未知的胰岛素分泌缺陷。我们未发现 HNF-1 α、-1 β、-4 α、IPF-1、ISL-1、BEAT2/NeuroD1、PAX4 和胰淀素基因有任何突变。 结论 我们报告了一例 PAX6 基因突变伴早发性糖尿病和无虹膜的病例。她父母的胰岛素分泌能力低，表明她的胰岛素分泌缺陷不仅是PAX6突变的结果，而且是从父母遗传的其他遗传因素造成的。
Background Paired box gene 6 (PAX6) is a transcription factor involved in eye development. Mutations of PAX6 cause congenital eye anomalies, such as aniridia. PAX6 is also involved in the development of the endocrine pancreas, and reported to be a genetic factor common to aniridia and glucose intolerance, although the latter is usually mild. Here, we describe a case of PAX6 mutation with early-onset diabetes mellitus.Case report A 27-year-old woman was referred to our clinic. She was diagnosed having diabetes at the age of 15 with negative glutamic acid decarboxylase (GAD) antibody. Insulin treatment was started at age 24. Because she had aniridia, PAX6 gene mutation was investigated and a heterozygous 2-bp deletion (c.402del2) was identified. Her parents did not have aniridia and PAX6 mutations. Heterozygous PAX6 mutation may cause glucose intolerance. However, cases of early-onset diabetes mellitus have not been reported. Her parents did not have diabetes, but their insulinogenic indices were low (0.25 and 0.3, respectively). We thought her early-onset diabetes was partly as a result of PAX6 mutation and partly because of an unknown insulin secretory defect inherited from her parents. We could not find any mutations in HNF-1 alpha, -1 beta, -4 alpha, IPF-1, ISL-1, BEAT2/NeuroD1, PAX4, and amylin genes.Conclusions We report a case of PAX6 gene mutation with early-onset diabetes mellitus and aniridia. Low insulin secretory capacity in her parents suggested that her insulin secretory defect is as a result of not only PAX6 mutation but other genetic factors inherited from her parents.