Clinical and genetic features of cervical dystonia in a large multicenter cohort.
Clinical and genetic features of cervical dystonia in a large multicenter cohort.
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DOI：
10.1212/nxg.0000000000000069
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发表时间：
2016-06
期刊：
影响因子：
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通讯作者：
Stover NP
中科院分区：
文献类型：
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作者：
LeDoux MS;Vemula SR;Xiao J;Thompson MM;Perlmutter JS;Wright LJ;Jinnah HA;Rosen AR;Hedera P;Comella CL;Weissbach A;Junker J;Jankovic J;Barbano RL;Reich SG;Rodriguez RL;Berman BD;Chouinard S;Severt L;Agarwal P;Stover NP
描述颈肌张力障碍 (CD) 的临床和遗传特征。本研究纳入了肌张力障碍联盟生物样本库 (NCT01373424) 中初始表现为 CD 的参与者 (n = 1,000)。数据摄入包括人口统计、家族史和全球肌张力障碍评定量表。对参与者进行了 GNAL、THAP1 和 TOR1A 外显子 5 的序列变异 (SV) 筛查。大多数参与者是白人（95%）和女性（75%）。平均发病年龄和病程分别为 45.5 ± 13.6 岁和 14.6 ± 11.8 岁。在评估时，68.5% 的患者受累仅限于颈部、肩部和近臂，而 47.4% 的患者肌张力障碍仅限于颈部。其余 31.5% 的个体表现出更广泛的解剖分布。 62% 的患者出现头部震颤。头部震颤和喉肌张力障碍在女性中更为常见。 32% 的参与者报告有精神合并症，主要是抑郁和焦虑，并且在女性中更为常见。分别有 14%、11% 和 29% 的患者有肌张力障碍、帕金森病和震颤家族史。在 8 名参与者 (0.8%) 中发现了 THAP1、TOR1A 和 GNAL 的致病性或可能致病性 SV。两个人在 TOR1A 的外显子 5 中携带新型错义 SV。在 4% 的队列中发现了 THAP1 和 GNAL 中的同义和非编码 SV。头部震颤、喉肌张力障碍和精神合并症在女性 CD 患者中更为常见。 GNAL、THAP1 和 TOR1A 的编码和非编码变异对 CD 的发病机制贡献不大。
To characterize the clinical and genetic features of cervical dystonia (CD). Participants enrolled in the Dystonia Coalition biorepository (NCT01373424) with initial manifestation as CD were included in this study (n = 1,000). Data intake included demographics, family history, and the Global Dystonia Rating Scale. Participants were screened for sequence variants (SVs) in GNAL, THAP1, and Exon 5 of TOR1A. The majority of participants were Caucasian (95%) and female (75%). The mean age at onset and disease duration were 45.5 ± 13.6 and 14.6 ± 11.8 years, respectively. At the time of assessment, 68.5% had involvement limited to the neck, shoulder(s), and proximal arm(s), whereas 47.4% had dystonia limited to the neck. The remaining 31.5% of the individuals exhibited more extensive anatomical spread. A head tremor was noted in 62% of the patients. Head tremor and laryngeal dystonia were more common in females. Psychiatric comorbidities, mainly depression and anxiety, were reported by 32% of the participants and were more common in females. Family histories of dystonia, parkinsonian disorder, and tremor were present in 14%, 11%, and 29% of the patients, respectively. Pathogenic or likely pathogenic SVs in THAP1, TOR1A, and GNAL were identified in 8 participants (0.8%). Two individuals harbored novel missense SVs in Exon 5 of TOR1A. Synonymous and noncoding SVs in THAP1 and GNAL were identified in 4% of the cohort. Head tremor, laryngeal dystonia, and psychiatric comorbidities are more common in female participants with CD. Coding and noncoding variants in GNAL, THAP1, and TOR1A make small contributions to the pathogenesis of CD.