Clinical findings of autosomal-dominant striatal degeneration and PDE8B mutation screening in parkinsonism and related disorders
Clinical findings of autosomal-dominant striatal degeneration and PDE8B mutation screening in parkinsonism and related disorders
复制标题
帕金森病及相关疾病常染色体显性纹状体变性和 PDE8B 突变筛查的临床结果
DOI：
10.1016/j.parkreldis.2019.11.002
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发表时间：
2019
影响因子：
4.1
通讯作者：
Wang Junling
中科院分区：
文献类型：
--
作者：
Ni Jie;Yi Xiaoping;Liu Zhen;Sun Weining;Yuan Yanchun;Yang Jie;Jiang Hong;Shen Lu;Tang Beisha;Liu Yunhai;Wang Junling
常染色体显性遗传性纹状体变性(ADSD)是一种罕见的由磷酸二酯酶8B(PDE8B)基因突变引起的神经退行性运动障碍。目的总结一个中国人常染色体显性遗传性纹状体变性(ADSD)家系的临床和影像特征，探讨PDE8B基因突变是否与帕金森病(PD)或帕金森病相关。从1714例PD或帕金森综合征患者和1039名对照的全外显子测序数据集中寻找PDE8B罕见的潜在致病变异。结果1名患者和1名症状前携带者的PDE8B(p.E102X)无义突变证实了ADSD的诊断。临床上，患者表现为进行性帕金森综合征，没有震颤和共济失调表型。神经影像显示患者纹状体T1加权像上信号不均匀增强，但症状前携带者的信号降低。弥散张量成像(DTI)显示白质纤维分布紊乱，尤其是豆状核与尾状核之间，患者较症状前携带者更为明显。根据ADSD中报道的功能预测和突变类型，在1714名患者中，发现了3个不太可能导致帕金森综合征表型的PDE8B错义变异。结论首次描述了ADSD中典型的共济失调表型。DTI扫描显示白质纤维完整性丧失。在我们的帕金森病或帕金森病患者队列中没有发现PDE8B突变。
BackgroundAutosomal-dominant striatal degeneration (ADSD) is a rare neurodegenerative movement disorder caused by mutations in the Phosphodiesterase 8B (PDE8B) gene.ObjectiveTo summarize the clinical and imaging features of a Chinese ADSD family and determine whether mutations inPDE8Bare associated with Parkinson's disease (PD) or Parkinsonism.MethodsClinical, imaging and genetic findings in a Chinese ADSD family are reported. Rare, potentially pathogenic variants inPDE8Bwere searched in whole-exome sequencing datasets from 1714 PD or parkinsonism patients and 1039 controls.ResultsAn ADSD diagnosis was confirmed by a nonsense mutation inPDE8B(p.E102X) in a patient and a presymptomatic carrier. Clinically, the patient exhibited progressive parkinsonism without tremor and ataxia phenotype. Neuroimaging showed an inhomogeneous increased signal in the patient's striatum on T1-weighted images but a decreased signal in the presymptomatic carrier. Diffusion tensor imaging (DTI) showed a disturbance in the white matter fiber distribution, especially between the lentiform nucleus and caudate nucleus, which was more prominent in the patient than in the presymptomatic carrier. Within the 1714 patients, threePDE8Bmissense variants were identified that were unlikely to be the cause of the parkinsonism phenotype according to the functional prediction and mutation types reported in ADSD.ConclusionsFor the first time, we described the typical ataxia phenotype in ADSD. A loss of white matter fiber integrity was shown on DTI scanning. No causativePDE8Bmutation was discovered in our cohort of PD or Parkinsonism patients.