Axonal neuropathy with unusual pattern of amyotrophy and alacrima associated with a novel AAAS mutation p.Leu430Phe
Axonal neuropathy with unusual pattern of amyotrophy and alacrima associated with a novel AAAS mutation p.Leu430Phe
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DOI：
10.1038/ejhg.2008.132
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发表时间：
2008-12-01
影响因子：
5.2
通讯作者：
Huebner, Angela
中科院分区：
文献类型：
--
作者：
Koehler, Katrin;Brockmann, Knut;Huebner, Angela
Triple A 综合征是由 AAAS 基因的常染色体隐性遗传突变引起的，其特征是失弛缓症、流泪症和肾上腺功能不全以及进行性神经功能障碍。我们报道了一名 14 岁女孩，她患有缓慢进行性轴突运动神经病，伴有小鱼际和小腿明显的肌肉萎缩以及泪液分泌。 AAAS 基因的突变分析揭示了一种复合杂合突变：先前报道过的外显子 2 中的 c.251G>A 突变，以及外显子 14 中的新 c.1288C>T 突变。在转录水平上，c.251G>A 转变导致该 RNA 链的异常剪接和衰变，因此特定的临床情况源自新的 c.1288C>T 突变。 1288C>T，（p.Leu430Phe，L430F）半合子形式突变。通过转染实验，我们证明 GFP-ALADIN(L430F) 正确定位到核孔复合物。因此，我们得出结论，该点突变损害了核孔处的 ALADIN 功能。
The triple A syndrome is caused by autosomal recessively inherited mutations in the AAAS gene and is characterized by achalasia, alacrima and adrenal insufficiency as well as progressive neurological impairment. We report on a 14-year-old girl with slowly progressive axonal motor neuropathy with conspicuous muscle wasting of hypothenars and calves as well as alacrima. The mutation analysis of the AAAS gene revealed a compound heterozygous mutation: a c.251G>A mutation in exon 2 that had been reported previously, and a novel c.1288C>T mutation in exon 14. At the transcriptional level, the c.251G>A transition results in an aberrant splicing and decay of this RNA strand so that the particular clinical picture results from the novel c. 1288C>T, (p.Leu430Phe, L430F) mutation in a hemizygous form. With transfection experiments, we demonstrate that GFP-ALADIN(L430F) correctly localizes to nuclear pore complexes. Therefore, we conclude that this point mutation impairs ALADIN function at the nuclear pore.