Johnson Janel O, Stevanin Giovanni, van de Leemput Joyce, Hernandez Dena G, Arepalli Sampath, Forlani Sylvie, Zonozi Reza, Gibbs J Raphael, Brice Alexis, Durr Alexandra, Singleton Andrew B
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA; Department of Molecular Neuroscience and Reta Lila Weston Institute of Neurological Studies, Institute of Neurology, University College London, Queen Square, London, UK.
Mov Disord. 2015 Feb;30(2):262-6. doi: 10.1002/mds.26059. Epub 2014 Dec 27.
The autosomal dominant spinocerebellar ataxias are most commonly caused by nucleotide repeat expansions followed by base-pair changes in functionally important genes. Structural variation has recently been shown to underlie spinocerebellar ataxia types 15 and 20.
We applied single-nucleotide polymorphism (SNP) genotyping to determine whether structural variation causes spinocerebellar ataxia in a family from France.
We identified an approximately 7.5-megabasepair duplication on chromosome 11q21-11q22.3 that segregates with disease. This duplication contains an estimated 44 genes. Duplications at this locus were not found in control individuals.
We have identified a new spastic ataxia syndrome caused by a genomic duplication, which we have denoted as spinocerebellar ataxia type 39. Finding additional families with this phenotype will be important to identify the genetic lesion underlying disease.
常染色体显性遗传性脊髓小脑共济失调最常见的病因是核苷酸重复序列扩展，随后是功能重要基因中的碱基对变化。最近研究表明，结构变异是脊髓小脑共济失调15型和20型的病因。
我们应用单核苷酸多态性（SNP）基因分型来确定结构变异是否导致来自法国一个家系的脊髓小脑共济失调。
我们在11号染色体q21 - 11q22.3区域发现了一个约750万碱基对的重复，该重复与疾病共分离。这个重复区域估计包含44个基因。在对照个体中未发现该位点的重复。
我们发现了一种由基因组重复引起的新的痉挛性共济失调综合征，我们将其命名为脊髓小脑共济失调39型。找到更多具有这种表型的家系对于确定疾病潜在的遗传损伤很重要。
