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Am J Hum Genet. 2012 Sep 7;91(3):548-52. doi: 10.1016/j.ajhg.2012.07.018.

VAMP1 mutation causes dominant hereditary spastic ataxia in Newfoundland families.

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The Centre of Excellence in Neurosciences, Centre Hospitalier de l'Université de Montréal Research Center, Université de Montréal, Montréal, QC H2L 2W5, Canada.


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, 50 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.

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