Clinical Application of Whole-Exome Sequencing A Novel Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay Sequence Variation in a Child With Ataxia
Clinical Application of Whole-Exome Sequencing A Novel Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay Sequence Variation in a Child With Ataxia
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DOI：
10.1001/jamaneurol.2013.247
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发表时间：
2013-06-01
期刊：
影响因子：
29
通讯作者：
Chung, Wendy K.
中科院分区：
文献类型：
--
作者：
Liew, Wendy K. M.;Ben-Omran, Tawfeg;Chung, Wendy K.
重要性：儿童共济失调是一个诊断挑战。除了共济失调的更常见的后天原因外，还有50多种与共济失调相关的遗传性疾病。我们的目标是突出全外显子组测序作为一个快速发展的临床工具，用于诊断孟德尔疾病，我们说明了这一点在一个单一的情况下，一个新的序列变异的SACS gene.Observations的报告：一个4岁的女孩提出了延迟粗大运动发育，共济失调，多发性神经病。遗传性和获得性共济失调常见病因的初步检测结果并不明确。全外显子组测序显示了一种新的移码纯合序列变异的SACS基因，符合诊断常染色体隐性遗传痉挛性共济失调的Charlevoix-Saguenay.Conclusions：全外显子组测序是一个强大的临床工具，已越来越多地用于协助诊断孟德尔疾病。它提供了一种具有成本效益，高效和快速的方法来进行临床诊断，在某些情况下，可能是唯一的诊断方法。
Importance: Ataxia in children is a diagnostic challenge. Besides the more common acquired causes of ataxia, there are more than 50 inherited disorders associated with ataxia. Our objective was to highlight whole-exome sequencing as a rapidly evolving clinical tool for diagnosis of mendelian disorders, and we illustrate this in the report of a single case of a novel sequence variation in the SACS gene.Observations: A 4-year-old girl presented with delayed gross motor development, ataxia, and polyneuropathy. Results of initial testing for the common causes of inherited and acquired ataxia were unrevealing. Whole-exome sequencing showed a novel frameshift homozygous sequence variation in the SACS gene, consistent with the diagnosis of autosomal recessive spastic ataxia of Charlevoix-Saguenay.Conclusions: Whole-exome sequencing is a powerful clinical tool that has been increasingly used to assist in the diagnosis of mendelian disorders. It provides a cost-effective, efficient, and expedited approach to making a clinical diagnosis and, in some cases, may be the only way to make a diagnosis.