INSERM U, Paris, France.
Acta Neurol Scand. 2012 Feb;125(2):116-22. doi: 10.1111/j.1600-0404.2011.01504.x. Epub 2011 Mar 21.
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.
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.
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.
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%.
尽管挪威常染色体显性小脑共济失调（ADCA）的患病率与其他欧洲国家相似，但只有不到 10%的家族可归因于 CAG 三核苷酸扩展。我们希望在显性共济失调人群中发现 SCA14 的存在，并描述其表型。
我们对一个大型的显性小脑共济失调队列进行了 PRKCG 基因突变筛查。根据标准的共济失调患者临床方案对患者进行评估。
在两个家族中发现了一种新的突变，即第 139 密码子处的 C 到 A 颠换，导致组氨酸突变为谷氨酰胺，该突变位于基因的高度保守区域。该突变完全与受累家族成员共分离，在 576 个对照染色体中未发现。遗传分析显示这两个家族之间三个微卫星标记的常见等位基因，提示存在共享的祖先染色体。受累者表现出一种轻度、进行性缓慢的小脑综合征，包括步态和肢体共济失调以及扫视追踪和头部震颤。发病年龄从 10 岁到 45 岁不等。
这些是来自斯堪的纳维亚的第一批 SCA14 家族报告，也是 PRKCG 基因中的一个新突变。在挪威显性共济失调队列中的发生率为 3.5%。
