Neurological Sciences ( IF 3.3 ) Pub Date : 2020-10-13 , DOI: 10.1007/s10072-020-04778-8 Relu Cocoș 1 , Florina Raicu 1, 2 , Ovidiu Lucian Băjenaru 3, 4 , Iulia Olaru 3, 5 , Laura Dumitrescu 3, 5 , Bogdan Ovidiu Popescu 3, 5, 6
Background
Isolated focal dystonia (IFD) is a heterogeneous group of potentially invalidating movement disorders. The etiopathogenesis is complex, both genetic and environmental factors playing a role, but remains elusive. The CACNA1B gene codes for the N-type neuronal voltage-gated calcium channels CaV2.2, which may play a role in the development of some IFD.
Methods
We analyzed samples from the GENDYS cohort for mutations in CACNA1B gene, using targeted next-generation sequencing (NGS).
Results
The GENDYS cohort consists of 120 people with adult-onset IFD (cervical dystonia 47.5%, blepharospasm 47.2%, others 8.3%). Of these, 35% had subsequent topographical extension. Average age at onset was 42 and average disease durations 8 years. Targeted NGS revealed a novel frameshift mutation c.2291AGG > A, in exon 19, and a previously reported variant, c.6834T > G, in exon 47.
Conclusion
Our findings suggest that disease-causing mutations in CACNA1B gene may be involved in the development of some adult-onset IFD. To our knowledge, this is the first study that identified a disease-causing CACNA1B gene mutation in association with adult-onset IFD.
中文翻译:
成人发病孤立局灶性肌张力障碍中的 CACNA1B 基因变异
背景
孤立的局灶性肌张力障碍 (IFD) 是一组可能导致无效的运动障碍。发病机制很复杂,遗传和环境因素都起作用,但仍然难以捉摸。CACNA1B基因编码N型神经元电压门控钙通道CaV2.2,可能在某些IFD的发生中起作用。
方法
我们使用靶向二代测序 (NGS) 分析了 GENDYS 队列中的 CACNA1B 基因突变样本。
结果
GENDYS 队列由 120 名成人 IFD 患者组成(宫颈肌张力障碍 47.5%,眼睑痉挛 47.2%,其他 8.3%)。其中,35% 有随后的地形扩展。平均发病年龄为 42 岁,平均病程为 8 年。靶向 NGS 在外显子 19 中发现了一个新的移码突变 c.2291AGG > A,在外显子 47 中发现了一个先前报道的变体 c.6834T > G。
结论
我们的研究结果表明,CACNA1B 基因的致病突变可能与一些成人发病的 IFD 的发展有关。据我们所知,这是第一项确定与成人发病的 IFD 相关的致病 CACNA1B 基因突变的研究。