Castro-Fernández Cristina, Arias Manuel, Blanco-Arias Patricia, Santomé-Collazo Luis, Amigo Jorge, Carracedo Ángel, Sobrido Maria-Jesús
Instituto de Investigación Sanitaria de Santiago-IDIS, Spain; Grupo de Medicina Xenómica, CIBERER, Universidade de Santiago de Compostela, Spain.
Instituto de Investigación Sanitaria de Santiago-IDIS, Spain; Servicio de Neurología, Complejo Hospitalario de Santiago de Compostela, Spain.
Appl Transl Genom. 2015 Jun 26;5:33-6. doi: 10.1016/j.atg.2015.05.005. eCollection 2015 Jun 1.
Next generation sequencing (NGS) is transforming the diagnostic approach for neurological disorders, since it allows simultaneous analysis of hundreds of genes, even based on just a broad, syndromic patient categorization. However, such an approach bears a high risk of incidental and uncertain genetic findings. We report a patient with spastic paraplegia whose comprehensive neurological and imaging examination raised a high clinical suspicion of SPG11. Thus, although our NGS pipeline for this group of disorders includes gene panel and exome sequencing, in this sample only the spatacsin gene region was captured and subsequently searched for mutations. Two probably pathogenic variants were quickly and clearly identified, confirming the diagnosis of SPG11. This case illustrates how combination of expert clinical characterization with highly oriented NGS protocols leads to a fast, cost-efficient diagnosis, minimizing the risk of findings with unclear significance.
下一代测序（NGS）正在改变神经系统疾病的诊断方法，因为它能够同时分析数百个基因，甚至仅基于宽泛的综合征患者分类即可。然而，这种方法存在发现偶然和不确定基因结果的高风险。我们报告了一名患有痉挛性截瘫的患者，其全面的神经学和影像学检查高度怀疑患有SPG11。因此，尽管我们针对这组疾病的NGS流程包括基因panel和外显子组测序，但在该样本中仅捕获了spatacsin基因区域并随后搜索突变。很快就明确鉴定出两个可能的致病变异，证实了SPG11的诊断。该病例说明了专家临床特征与高度定向的NGS方案相结合如何导致快速、经济高效的诊断，将具有不明确意义的发现风险降至最低。
