Hereditary spastic paraplegia is a novel phenotype for germline de novo ATP1A1 mutation
Hereditary spastic paraplegia is a novel phenotype for germline de novo ATP1A1 mutation
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DOI：
10.1111/cge.13668
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发表时间：
2019-12-05
影响因子：
3.5
通讯作者：
Nicita, Francesco
中科院分区：
文献类型：
--
作者：
Stregapede, Fabrizia;Travaglini, Lorena;Nicita, Francesco
ATP 1A 1编码Na+/K+-ATP酶的α-1亚型，最近报道ATP 1A 1的显性突变可导致轴突型至中间型Charcot-Marie-Tooth病（即CMT 2DD）和低镁血症、顽固性癫痫发作和严重智力残疾综合征。在这里，我们描述了第一例遗传性痉挛性截瘫（HSP）引起的一种新的从头（p.L337P）变异ATP 1A 1。我们提供的证据与功能和同源性建模研究这种变体的致病作用。这一发现扩展了ATP 1A 1相关疾病的表型谱，为HSP的更大遗传难题增加了一块，并增加了对遗传性轴突病（即CMT和HSP）分子机制的了解。
Dominant mutations in ATP1A1, encoding the alpha-1 isoform of the Na+/K+-ATPase, have been recently reported to cause an axonal to intermediate type of Charcot-Marie-Tooth disease (ie, CMT2DD) and a syndrome with hypomagnesemia, intractable seizures and severe intellectual disability. Here, we describe the first case of hereditary spastic paraplegia (HSP) caused by a novel de novo (p.L337P) variant in ATP1A1. We provide evidence for the causative role of this variant with functional and homology modeling studies. This finding expands the phenotypic spectrum of the ATP1A1-related disorders, adds a piece to the larger genetic puzzle of HSP, and increases knowledge on the molecular mechanisms underlying inherited axonopathies (ie, CMT and HSP).