Kay Denise M, Zabetian Cyrus P, Factor Stewart A, Nutt John G, Samii Ali, Griffith Alida, Bird Tom D, Kramer Patricia, Higgins Donald S, Payami Haydeh
Genomics Institute, Wadsworth Center, New York State Department of Health, Albany, 12201, USA.
Mov Disord. 2006 Apr;21(4):519-23. doi: 10.1002/mds.20751.
The G2019S mutation in the LRRK2 gene is reportedly a common cause of familial Parkinson's disease (PD) and may also have a significant role in nonfamilial PD. The objective of this study was to assess mutation carrier frequency in PD patients from movement disorder clinics in the United States, stratified by family history, age at onset, and geography; to determine carrier frequency in a large and well-characterized control population; to examine segregation of mutation in families of patients; and to correlate genotype with clinical phenotype. One thousand four hundred twenty-five unrelated PD patients from movement disorder clinics in Oregon, Washington, and New York and 1,647 unrelated controls were studied. The G2019S mutation was detected using a TaqMan assay and verified by sequencing. Eighteen of 1,425 patients and one of 1,647 controls had the mutation. Carrier frequency (+/- 2SE) in patients was 0.013 +/- 0.006 overall, 0.030 +/- 0.019 in familial PD, 0.007 +/- 0.005 in nonfamilial PD, 0.016 +/- 0.013 in early-onset PD, and 0.012 +/- 0.007 in late-onset PD. Geographic differences were insignificant. Age at onset of mutation carriers ranged from 28 to 71 years. Mutation carriers were clinically indistinguishable from idiopathic PD. LRRK2 G2019S is the single most common pathogenic mutation linked to neurodegenerative disease to date.
据报道，LRRK2基因中的G2019S突变是家族性帕金森病（PD）的常见病因，在非家族性PD中可能也起重要作用。本研究的目的是评估来自美国运动障碍诊所的PD患者中突变携带者的频率，按家族史、发病年龄和地理位置分层；确定在一个大规模且特征明确的对照人群中的携带者频率；检查患者家族中突变的分离情况；并将基因型与临床表型相关联。对来自俄勒冈州、华盛顿州和纽约州运动障碍诊所的1425例无亲缘关系的PD患者和1647例无亲缘关系的对照进行了研究。使用TaqMan分析检测G2019S突变并通过测序进行验证。1425例患者中有18例、1647例对照中有1例携带该突变。患者中携带者频率（±2SE）总体为0.013±0.006，家族性PD中为0.030±0.019，非家族性PD中为0.007±0.005，早发性PD中为0.016±0.013，晚发性PD中为0.012±0.007。地理差异不显著。突变携带者的发病年龄在28至71岁之间。突变携带者在临床上与特发性PD无法区分。LRRK2 G2019S是迄今为止与神经退行性疾病相关的最常见的单一致病突变。
