SCA14 in Norway, two families with autosomal dominant cerebellar ataxia and a novel mutation in the PRKCG gene
SCA14 in Norway, two families with autosomal dominant cerebellar ataxia and a novel mutation in the PRKCG gene
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DOI：
10.1111/j.1600-0404.2011.01504.x
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发表时间：
2012-02-01
影响因子：
3.5
通讯作者：
Tallaksen, C. M. E.
中科院分区：
文献类型：
--
作者：
Koht, J.;Stevanin, G.;Tallaksen, C. M. E.
目的：尽管挪威的常染色体显性小脑性共济失调（ADCA）患病率与其他欧洲国家相似，但只有不到10%的家庭可以用CAG三核苷酸扩增来解释。我们希望找到SCA14在共济失调显性人群中的发生率，并描述其表型。方法：我们筛选了大量显性小脑性共济失调患者的PRKCG基因突变。根据共济失调患者的标准临床方案对患者进行评估。结果在两个家族中发现了一个新的突变，即C - to - A翻转，将位于该基因高度关注区域的密码子139上的组氨酸转变为谷氨酰胺。它与受影响的家族成员完全共分离，在576条对照染色体中未见。遗传分析显示，这两个家族在三个微卫星标记上有共同的等位基因，表明它们具有共同的祖先染色体。受影响的受试者表现出轻微的、缓慢进展的小脑综合征，包括步态和肢体共济失调、跳眼追逐和头部震颤。发病年龄在10 - 45岁之间。结论：这是斯堪的纳维亚半岛报道的第一个SCA14家族和PRKCG基因的新突变。挪威显性共济失调队列的发生率为3.5%。
Objectives - Despite a similar prevalence of autosomal dominant cerebellar ataxia (ADCA) in Norway compared to other European countries, less than 10% of the families are explained by the CAG trinucleotide expansions. We wanted to find the occurence of SCA14 in the dominant ataxia population and describe the phenotype. Methods - We screened a large dominant cerebellar ataxia cohort for mutations in the PRKCG gene. Patients were evaluated according to a standard clinical protocol for ataxia patients. Results A novel mutation was found in two families, a C to A transversion altering Histidine to a Glutamine at codon 139, located in a highly concerved region in the gene. It completely co-segregated with the affected family members and was not seen in 576 control chromosomes. Genetic analysis revealed common alleles at three microsatellite markers between these two families suggesting a shared ancestral chromosome. Affected subjects displayed a mild, slowly progressive cerebellar syndrome that included gait and limb ataxia and saccadic pursuit and head tremor in one. Age at onset ranged from 10 to 45 years. Conclusions - These are the first families with SCA14 reported from Scandinavia and a new mutation in the PRKCG gene. The occurrence in the Norwegian dominant ataxia cohort is 3.5%.