JM2, encoding a fork head-related protein, is mutated in X-linked autoimmunity-allergic disregulation syndrome
JM2, encoding a fork head-related protein, is mutated in X-linked autoimmunity-allergic disregulation syndrome
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DOI：
10.1172/jci11679
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发表时间：
2000-12-01
影响因子：
15.9
通讯作者：
Bowcock, AM
中科院分区：
文献类型：
--
作者：
Chatila, TA;Blaeser, F;Bowcock, AM
X-连锁自身免疫-变态反应性紊乱综合征(XLAAD)是一种X连锁的隐性免疫疾病，以多系统自身免疫为特征，尤其是迟发性1型糖尿病，与严重的特应性表现相关，包括湿疹、食物过敏和嗜酸性炎症。与过敏表型一致，XLAAD对两个家系的分析显示，患者T淋巴细胞明显向Th2表型倾斜。使用位置候选方法，我们已经在两个家族中发现了JM2的突变，JM2是Xp11.23上的一个基因，编码含有叉头域的蛋白。剪接连接点的一个点突变导致转录本编码缺乏叉头同源结构域的截短蛋白。另一个突变涉及框内3个碱基的缺失，预计会损害亮氨酸拉链二聚结构域的功能。我们的结果表明JM2在自身耐受和Th细胞分化中起着关键作用。
X-linked autoimmunity-allergic disregulation syndrome (XLAAD) is an X-linked recessive immunological disorder characterized by multisystem autoimmunity particularly tarry-onset type 1 diabetes mellitus, associated with manifestations of severe atopy including eczema, food allergy, and eosinophilic inflammation. Consistent with the allergic phenotype, analysis of two kindreds with XLAAD revealed marked skewing of patient T lymphocytes toward the Th2 phenotype. Using a positional-candidate approach, we have identified in both kindreds mutations in JM2, a gene on Xp11.23 that encodes a fork head domain-containing protein. One point mutation at a splice junction site results in transcripts that encode a truncated protein lacking the fork head homology domain. The other mutation involves an in-frame, 3-bp deletion that is predicted to impair the function of a leucine zipper dimerization domain. Our results point to a critical role for JM2 in self tolerance and Th cell differentiation.