PDF(Pubmed)
Abstract：
BACKGROUND: Autosomal recessive spastic ataxia ofCharlevoix-Saguenay (ARSACS) is a rare neurodegenerative disorder characterizedby early-onset cerebellar ataxia, peripheral sensorimotor neuropathy, and lowerlimb spasticity. We present clinical andgenetic data of the first Bulgarian patients diagnosed with ARSACS by wholeexome sequencing (WES).
METHODS: Variant filtering was performed usinglocally established pipeline and the selected variants were analysed by Sangersequencing. All patients underwent clinical examination and testingincluding the standard rating scales for spastic paraplegia and ataxia.
RESULTS: Five different SACS gene variants, three of which novel, have been identified inpatients from three different ethnic groups. In addition to the classicalclinical triad, brain MRI revealed cerebellar atrophy, linear pontineT2-hypointensities, and hyperintense rim lateral tothalamus combined with retinal nerve fiber layer thickening on opticcoherence tomography (OCT).
CONCLUSIONS: We expand the mutation, geographic, and phenotypic spectrum of ARSACS, adding Bulgaria to the world map of the disease, and drawing attention to the fact that it is still misdiagnosed. We demonstrated that brain MRI and OCT are necessary clinical tests for ARSACS diagnosis, even if one of the cardinal clinical features is lacking.
METHODS: Variant filtering was performed usinglocally established pipeline and the selected variants were analysed by Sangersequencing. All patients underwent clinical examination and testingincluding the standard rating scales for spastic paraplegia and ataxia.
RESULTS: Five different SACS gene variants, three of which novel, have been identified inpatients from three different ethnic groups. In addition to the classicalclinical triad, brain MRI revealed cerebellar atrophy, linear pontineT2-hypointensities, and hyperintense rim lateral tothalamus combined with retinal nerve fiber layer thickening on opticcoherence tomography (OCT).
CONCLUSIONS: We expand the mutation, geographic, and phenotypic spectrum of ARSACS, adding Bulgaria to the world map of the disease, and drawing attention to the fact that it is still misdiagnosed. We demonstrated that brain MRI and OCT are necessary clinical tests for ARSACS diagnosis, even if one of the cardinal clinical features is lacking.
摘要：
背景：Charlevoix-Saguenay常染色体隐性遗传性痉挛性共济失调（ARSACS）是一种罕见的神经退行性疾病，其特征是早发性小脑共济失调，周围感觉运动神经病,和下肢痉挛。我们提供了通过全外显子组测序（WES）诊断为ARSACS的第一批保加利亚患者的临床和遗传数据。
方法：使用本地建立的管道进行变体过滤，并通过Sangersequencing分析选择的变体。所有患者均接受了临床检查和测试，包括痉挛型截瘫和共济失调的标准评定量表。
结果：五种不同的SACS基因变异，其中三本小说，已经确定了来自三个不同种族的住院患者。除了经典的临床三合会，脑部MRI显示小脑萎缩,线性pontineT2-低张力，光学相干断层扫描（OCT）上的高信号边缘外侧丘脑结合视网膜神经纤维层增厚。
结论：我们扩展了突变，地理,和ARSACS的表型谱，将保加利亚添加到该疾病的世界地图中，并提请注意它仍然被误诊的事实。我们证明了脑部MRI和OCT是ARSACS诊断的必要临床测试，即使缺乏一个主要的临床特征。
方法：使用本地建立的管道进行变体过滤，并通过Sangersequencing分析选择的变体。所有患者均接受了临床检查和测试，包括痉挛型截瘫和共济失调的标准评定量表。
结果：五种不同的SACS基因变异，其中三本小说，已经确定了来自三个不同种族的住院患者。除了经典的临床三合会，脑部MRI显示小脑萎缩,线性pontineT2-低张力，光学相干断层扫描（OCT）上的高信号边缘外侧丘脑结合视网膜神经纤维层增厚。
结论：我们扩展了突变，地理,和ARSACS的表型谱，将保加利亚添加到该疾病的世界地图中，并提请注意它仍然被误诊的事实。我们证明了脑部MRI和OCT是ARSACS诊断的必要临床测试，即使缺乏一个主要的临床特征。
