A rare polyadenylation signal mutation of the FOXP3 gene (AAUAAA→AAUGAA) leads to the IPEX syndrome
A rare polyadenylation signal mutation of the FOXP3 gene (AAUAAA→AAUGAA) leads to the IPEX syndrome
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DOI：
10.1007/s002510100358
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发表时间：
2001-08-01
期刊：
影响因子：
3.2
通讯作者：
Chance, PF
中科院分区：
文献类型：
--
作者：
Bennett, CL;Brunkow, ME;Chance, PF
最近通过定位克隆鉴定了小鼠 scurfy 基因 Foxp3 及其人类直系同源物 FOXP3（映射到 Xp11.23-Xq13.3）。在 9 个 IPEX（免疫功能障碍、多内分泌病、肠病、X 连锁；OMIM 304930）家族中的 8 个受影响成员中发现了 FOXP3 基因的点突变和微缺失。我们评估了具有临床典型 IPEX 的谱系，其中未检测到 FOXP3 编码外显子的突变。我们对该谱系的重新评估确定了终止密码子后第一个聚腺苷酸化信号（AA 条下的 AAUAAA --> AAU (G)）内的 A -->G 转变。再过 5.1 kb 就没有遇到下一个聚腺苷酸化信号。在超过 212 个正常个体（类似于 318 个 X 染色体）中没有检测到这种转变，排除了罕见多态性的可能性。我们认为，这种突变是通过 FOXP3 基因信息的非特异性降解机制导致该家族 IPEX 的原因。
The mouse scurfy gene, Foxp3, and its human orthologue, FOXP3, which maps to Xp11.23-Xq13.3, were recently identified by positional cloning. Point mutations and microdeletions of the FOXP3 gene were found in the affected members of eight of nine families with IPEX (immune dysfunction, polyendocrinopathy, enteropathy, X-linked; OMIM 304930). We evaluated a pedigree with clinically typical IPEX in which mutations of the coding, exons of FOXP3 were not detected. Our reevaluation of this pedigree identified an A -->G transition within the first polyadenylation signal (AAUAAA --> AAU (G) under bar AA) after the stop codon. The next polyadenylation signal is not encountered for a further 5.1 kb. This transition was not detected in over 212 normal individuals (similar to 318 X chromosomes), excluding the possibility of a rare polymorphism. We suggest that this mutation is causal of IPEX in this family by a mechanism of nonspecific degradation of the FOXP3 gene message.