Clinical and pathological characteristics of patients with leucine-rich repeat kinase-2 mutations.
Clinical and pathological characteristics of patients with leucine-rich repeat kinase-2 mutations.
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DOI：
10.1002/mds.22096
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发表时间：
2009-01-15
影响因子：
8.6
通讯作者：
Giasson, Benoit I.
中科院分区：
文献类型：
--
作者：
Covy, Jason P.;Yuan, Wuxing;Waxman, Elisa A.;Hurtig, Howard I.;Van Deerlin, Vivianna M.;Giasson, Benoit I.
关键词：
LRRK 2的突变是帕金森病（PD）最常见的已知原因。从一个具有广泛尸检评估的队列中确定了2例新的LRRK 2突变PD患者。其中1例患者携带R793 M突变，并表现出典型的PD临床和病理特征。在第二例患者中发现了一种新的L1165 P突变。该患者具有PD的经典和病理学特征，但还出现了严重的神经心理学症状和痴呆，与海马结构中大量神经元缠结相关;特征与缠结主导型痴呆的继发诊断一致。这些患者中含有α-突触核蛋白的病理性内含物也在Ser-129处高度磷酸化，与其他特发性PD患者相似。这两名PD患者的特征还在于颞叶皮质中偶尔存在胞质TDP-43包涵体，这一发现在其他三名LRRK 2中G2019 S突变的患者中未观察到。这些发现扩展了可能与LRRK 2突变相关的临床和病理特征。
Mutations in LRRK2 are the single most common known cause of Parkinson's disease (PD). Two new PD patients with LRRK2 mutation were identified from a cohort with extensive post-mortem assessment. One of these patients harbors the R793M mutation and presented with the typical clinical and pathological features of PD. A novel L1165P mutation was identified in a second patient. This patient had the classical and pathological features of PD, but additionally developed severe neuropsychological symptoms and dementia associated with abundant neurofibrillary tangles in the hippocampal formation; features consistent with a secondary diagnosis of tangle-predominant dementia. α-Synuclein-containing pathological inclusions in these patients also were highly phosphorylated at Ser-129, similar to other patients with idiopathic PD. These two PD patients also were characterized by the presence of occasional cytoplasmic TDP-43 inclusions in the temporal cortex, a finding that was not observed in three other patients with the G2019S mutation in LRRK2. These findings extend the clinical and pathological features that may be associated with LRRK2 mutations.
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影响因子：
9.9
作者：
Chen-Plotkin, A. S.;Yuan, W.;Van Deerlin, V. M.
通讯作者：
Van Deerlin, V. M.
影响因子：
14.5
作者：
Berg, D;Schweitzer, KJ;Gasser, T
通讯作者：
Gasser, T
影响因子：
11.2
作者：
Funayama, M;Hasegawa, K;Obata, F
通讯作者：
Obata, F
影响因子：
11
作者：
Gaig, Carles;Marti, Maria Jose;Tolosa, Eduardo
通讯作者：
Tolosa, Eduardo
影响因子：
21.3
作者：
Fujiwara, H;Hasegawa, M;Iwatsubo, T
通讯作者：
Iwatsubo, T