成人起病的孤立性局灶性肌张力障碍中的CACNA1B基因变异
CACNA1B gene variants in adult-onset isolated focal dystonia.
作者信息
Cocoș Relu, Raicu Florina, Băjenaru Ovidiu Lucian, Olaru Iulia, Dumitrescu Laura, Popescu Bogdan Ovidiu
机构信息
Department of Medical Genetics, Carol Davila University of Medicine and Pharmacy, 37 Dionisie Lupu Str, 020021, Bucharest, Romania.
Francisc I. Rainer Anthropological Research Institute, Romanian Academy, 8 Eroii Sanitari Bld, 050474, Bucharest, Romania.
出版信息
Neurol Sci. 2021 Mar;42(3):1113-1117. doi: 10.1007/s10072-020-04778-8. Epub 2020 Oct 13.
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.
背景
孤立性局灶性肌张力障碍（IFD）是一组异质性的、可能导致功能丧失的运动障碍。其发病机制复杂，遗传和环境因素均起作用，但仍不明确。CACNA1B基因编码N型神经元电压门控钙通道CaV2.2，该通道可能在某些IFD的发病过程中发挥作用。
方法
我们使用靶向二代测序（NGS）分析了GENDYS队列中的样本，以检测CACNA1B基因的突变情况。
结果
GENDYS队列由120例成年起病的IFD患者组成（颈部肌张力障碍占47.5%，眼睑痉挛占47.2%，其他占8.3%）。其中，35%的患者随后出现了部位扩展。平均发病年龄为42岁，平均病程为8年。靶向NGS检测发现，外显子19中有一个新的移码突变c.2291AGG＞A，外显子47中有一个先前报道的变异c.6834T＞G。
结论
我们的研究结果表明，CACNA1B基因中的致病突变可能参与了某些成年起病的IFD的发病过程。据我们所知，这是第一项鉴定出与成年起病的IFD相关的致病CACNA1B基因突变的研究。
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