VAMP1 Mutation Causes Dominant Hereditary Spastic Ataxia in Newfoundland Families
VAMP1 Mutation Causes Dominant Hereditary Spastic Ataxia in Newfoundland Families
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DOI：
10.1016/j.ajhg.2012.07.018
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发表时间：
2012-09-07
影响因子：
9.8
通讯作者：
Rouleau, Guy A.
中科院分区：
文献类型：
--
作者：
Bourassa, Cynthia V.;Meijer, Inge A.;Rouleau, Guy A.
我们的小组以前描述和映射到染色体区域12p13的一种形式的显性遗传性痉挛性共济失调（HSA）在三个大纽芬兰（加拿大）的家庭。这份报告确定囊泡相关膜蛋白1（VAMP1），它编码一个关键的蛋白质突触胞吐，作为负责基因。总的来说，来自这些家族的SO受影响个体和来自安大略（加拿大）的三个独立先证者共享疾病表型以及破坏性VAMP1突变，其影响VAMP1同种型剪接的关键供体位点。这种突变导致神经系统中表达的唯一VAMP1同种型（VAMP1A）的丢失，从而突出了研究充分的VAMP1与神经系统疾病之间的关联。考虑到在这里检查的受影响个体中观察到的可变表型，我们认为应该在共济失调或痉挛性截瘫患者中检测VAMP1的突变。
Our group previously described and mapped to chromosomal region 12p13 a form of dominantly inherited hereditary spastic ataxia (HSA) in three large Newfoundland (Canada) families. This report identifies vesicle-associated membrane protein 1 (VAMP1), which encodes a critical protein for synaptic exocytosis, as the responsible gene. In total, SO affected individuals from these families and three independent probands from Ontario (Canada) share the disease phenotype together with a disruptive VAMP1 mutation that affects a critical donor site for the splicing of VAMP1 isoforms. This mutation leads to the loss of the only VAMP1 isoform (VAMP1A) expressed in the nervous system, thus highlighting an association between the well-studied VAMP1 and a neurological disorder. Given the variable phenotype seen in the affected individuals examined here, we believe that VAMP1 should be tested for mutations in patients with either ataxia or spastic paraplegia.