Mutations of the autoimmune regulator gene (AIRE), located on chromosome 21q22.3, are recognized as the cause of a rare monogenic organ-specific autoimmune disorder called autoimmune polyglandular syndrome type 1 (APS-1). Three major components of this syndrome include chronic mucocutaneous candidiasis (CMC), hypoparathyroidism, and adrenocortical failure. We report a 19-year-old girl, who was born in an Iranian Muslim family with a clinical diagnosis of APS-1. To identify the causative mutation, a direct sequencing of the entire AIRE gene sequence was performed by Sanger sequencing method. Three distinct variants were discovered, including c.1095 + 2 T > A, c.1197 T > C (rs1800521) and c.1578 T > C (rs1133779), in intron 9, exons 10 and 14 of the AIRE gene, respectively. To the best of our knowledge, this is the first report of an Iranian Muslim APS-1 patient with combination of these variations. In addition, the effect of c.1095 + 2 T > A mutation on AIRE mRNA expression was reported for the first time. This study expands the diversity of variants that could cause APS-1. More genetic studies are required to determine the exact frequency of these variants and their diagnostic significance.

中文翻译：

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自身免疫性多腺体综合征 1 型：病例报告


位于染色体 21q22.3 上的自身免疫调节基因 (AIRE) 的突变被认为是导致一种罕见的单基因器官特异性自身免疫性疾病，称为 1 型自身免疫性多腺体综合征 (APS-1) 的原因。该综合征的三个主要组成部分包括慢性皮肤粘膜念珠菌病 (CMC)、甲状旁腺功能减退症和肾上腺皮质功能衰竭。我们报告了一名 19 岁女孩，她出生在伊朗穆斯林家庭，临床诊断为 APS-1。为了确定致病突变，通过桑格测序方法对整个 AIRE 基因序列进行了直接测序。发现了三个不同的变异，包括 c.1095 + 2 T > A、c.1197 T > C (rs1800521) 和 c.1578 T > C (rs1133779)，分别位于 AIRE 基因的内含子 9、外显子 10 和 14 。据我们所知，这是伊朗穆斯林 APS-1 患者兼具这些变异的首例报告。此外，首次报道了c.1095+2T>A突变对AIRE mRNA表达的影响。这项研究扩大了可能导致 APS-1 的变异的多样性。需要更多的遗传学研究来确定这些变异的确切频率及其诊断意义。