Ross Owen A, Toft Mathias, Whittle Andrew J, Johnson Joseph L, Papapetropoulos Spiridon, Mash Deborah C, Litvan Irene, Gordon Mark F, Wszolek Zbigniew K, Farrer Matthew J, Dickson Dennis W
Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL 32224, USA.
Ann Neurol. 2006 Feb;59(2):388-93. doi: 10.1002/ana.20731.
The Lrrk2 kinase domain G2019S substitution is the most common genetic basis of familial and sporadic parkinsonism. Patients harboring the G2019S substitution usually present with clinical Parkinson's disease.
Herein, we report that the most common neuropathology of G2019S-associated Parkinson's disease is Lewy body disease.
Lrrk2 G2019S was observed in approximately 2% (n = 8) of our Parkinson's disease/Lewy body disease cases (n = 405). The mutation was also found in one control subject and one Alzheimer's disease patient, reflecting reduced penetrance.
Therapeutic strategies targeted at modulating Lrrk2 kinase activity may be important to treat patients with genetically defined familial or typical sporadic Parkinson's disease.
亮氨酸重复激酶2（Lrrk2）激酶结构域G2019S替代是家族性和散发性帕金森病最常见的遗传基础。携带G2019S替代的患者通常表现为临床帕金森病。
在此，我们报告G2019S相关帕金森病最常见的神经病理学是路易体病。
在我们的帕金森病/路易体病病例（n = 405）中，约2%（n = 8）观察到Lrrk2 G2019S。在一名对照受试者和一名阿尔茨海默病患者中也发现了该突变，反映出其外显率降低。
针对调节Lrrk2激酶活性的治疗策略对于治疗具有明确遗传背景的家族性或典型散发性帕金森病患者可能很重要。
