Positional cloning of the APECED gene
Positional cloning of the APECED gene
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DOI：
10.1038/ng1297-393
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发表时间：
1997-12-01
期刊：
影响因子：
30.8
通讯作者：
Shimizu, N
中科院分区：
文献类型：
--
作者：
Nagamine, K;Peterson, P;Shimizu, N
自身免疫性多腺体综合征I型（Autoimmune polyglandular syndrome type I，APS 1，又称APECED）是一种常染色体隐性遗传疾病，通过连锁研究定位于人类染色体21q22.3的D21 S49和D21 S171之间。我们从该区域分离出了一个新基因AIRE（自身免疫调节因子），该基因编码一种含有暗示转录因子的基序的蛋白质，包括两个锌指（PHD指）基序、一个富含脯氨酸的区域和三个LXXLL基序。在瑞士和芬兰的APECED患者中发现了两种突变，一种是将Arg 257（CGA）变为终止密码子（TGA）的C->T取代，另一种是将Lys 83（AAG）变为Glu密码子（GAG）的A->G取代。Arg 257 stop（R257 X）是芬兰APECED患者的主要突变，占研究的10/12等位基因。这些结果表明，该基因是负责APECED的发病机制。APECED缺陷基因的鉴定将有助于该疾病的基因诊断和潜在治疗，并进一步提高我们对自身免疫性疾病机制的认识。
Autoimmune polyglandular syndrome type I (APS 1, also called APECED) is an autosomal-recessive disorder that maps to human chromosome 21q22.3 between markers D21S49 and D21S171 by linkage studies. We have isolated a novel gene from this region, AIRE (autoimmune regulator), which encodes a protein containing motifs suggestive of a transcription factor including two zinc-finger (PHD-finger) motifs, a proline-rich region and three LXXLL motifs. Two mutations, a C-->T substitution that changes the Arg 257 (CGA) to a stop codon (TGA) and an A-->G substitution that changes the Lys 83 (AAG) to a Glu codon (GAG), were found in this novel gene in Swiss and Finnish APECED patients. The Arg257stop (R257X) is the predominant mutation in Finnish APECED patients, accounting for 10/12 alleles studied. These results indicate that this gene is responsible for the pathogenesis of APECED. The identification of the gene defective in APECED should facilitate the genetic diagnosis and potential treatment of the disease and further enhance our general understanding of the mechanisms underlying autoimmune diseases.