The phenotypic spectrum of rapid-onset dystonia-parkinsonism (RDP) and mutations in the ATPIA3 gene
The phenotypic spectrum of rapid-onset dystonia-parkinsonism (RDP) and mutations in the ATPIA3 gene
复制标题
DOI：
10.1093/brain/awl340
复制
发表时间：
2007-03-01
期刊：
影响因子：
14.5
通讯作者：
Ozelius, Laurie J.
中科院分区：
文献类型：
--
作者：
Brashear, Allison;Dobyns, William B.;Ozelius, Laurie J.
快速发作性肌张力障碍-帕金森综合征（RDP）（也称为DYT 12）的特征是肌张力障碍和帕金森综合征的突然发作，由ATP 1A 3基因突变引起。我们获得了来自21个“可能的”RDP家族的49名受试者的临床数据和ATP 1A 3基因测序，并进行了基因型-表型分析。在新的家庭研究中，只有14个家庭中的3个（21%）表现出ATP 1A 3基因的突变，但没有发现新的突变，超出了我们先前的报告6。将这些突变与先前报道的家族进行比较，我们在10个家族的36个个体中发现了突变，其中包括4个从头突变，并在11个家族的13个个体中排除了突变。突变阳性患者的表型包括突然发作的肌张力障碍，具有帕金森综合征的特征，吻尾梯度和突出的延髓发现。在一些突变携带者中发现的其他特征包括常见的触发因素报告，发作时轻微或无震颤，原发性发作前偶尔轻度肢体肌张力障碍，对多巴胺能药物缺乏反应，生活后期症状罕见突然恶化，症状在一个月内稳定，总体改善极小。在比较ATP 1A 3突变阳性和阴性患者中，我们发现症状发作时的震颤、反向的喙尾梯度和显著的肢体疼痛排除了RDP的诊断。不需要阳性家族史。当突然发作，吻尾梯度和突出的延髓发现时，建议对ATP 1A 3基因进行基因检测。
Rapid-onset dystonia-parkinsonism (RDP) (also known as DYT12) is characterized by the abrupt onset of dystonia and parkinsonism and is caused by mutations in the ATP1A3 gene. We obtained clinical data and sequenced the ATP1A3 gene in 49 subjects from 21 families referred with 'possible' RDP, and performed a genotype-phenotype analysis. Of the new families referred for study only 3 of 14 families (21%) demonstrated amutation in the ATP1A3 gene, but no new mutations were identified beyond our earlier report of 6. Adding these to previously reported families, we found mutations in 36 individuals from 10 families including 4 de novo mutations and excluded mutations in 13 individuals from 11 families. The phenotype in mutation positive patients included abrupt onset of dystonia with features of parkinsonism, a rostrocaudal gradient, and prominent bulbar findings. Other features found in some mutation carriers included common reports of triggers, minimal or no tremor at onset, occasional mild limb dystonia before the primary onset, lack of response to dopaminergic medications, rare abrupt worsening of symptoms later in life, stabilization of symptoms within a month and minimal improvement overall. In comparing ATP1A3 mutation positive and negative patients, we found that tremor at onset of symptoms, a reversed rostrocaudal gradient, and significant limb pain exclude a diagnosis of RDP. A positive family history is not required. Genetic testing for the ATP1A3 gene is recommended when abrupt onset, rostrocaudal gradient and prominent bulbar findings are present.