Neurological Clinical Research Unit, Instituto de Medicina Molecular, Lisbon School of Medicine, Lisbon, Portugal.
Parkinsonism Relat Disord. 2010 May;16(4):237-42. doi: 10.1016/j.parkreldis.2009.11.004. Epub 2009 Nov 30.
The LRRK2 G2019S mutation is the most frequent known cause of familial and sporadic Parkinson's disease. Knowledge of its worldwide frequency distribution is essential for clinical and molecular research as well as genetic counseling.
To conduct a systematic review of the reported frequency of G2019S in different populations and to assess critically the quality of the clinical studies.
We conducted a systematic review of all published papers on G2019S frequency in homogeneous ethnic groups or sub-groups of patients. Selected papers were analyzed for methodological quality.
68 studies from 32 countries were included in the analysis. A heterogeneous distribution was observed with high frequencies in North African Arab countries, the Middle East, southern Europe, North American Ashkenazi Jewish populations and in South American countries with known European ethnic influence. Frequencies ranged from the no cases to 35.7% in sporadic and 42% in familial North-African Arab patients. Only one paper from one sub-Saharan country was found. Methodological pitfalls were identified.
Estimated frequencies were found to be variable, which may reflect ethnic differences and methodological discrepancies. We make recommendations on the methods of selection of participants and on the definition of familial Parkinson's disease to improve the quality of frequency studies on LRRK2 mutations.
LRRK2 G2019S 突变是已知最常见的家族性和散发性帕金森病的原因。了解其在世界范围内的频率分布对于临床和分子研究以及遗传咨询至关重要。
对不同人群中报告的 G2019S 频率进行系统综述，并批判性评估临床研究的质量。
我们对所有关于同质种族群体或患者亚组中 G2019S 频率的已发表论文进行了系统综述。对选定的论文进行了方法学质量分析。
从 32 个国家的 68 项研究中纳入了分析。观察到分布不均，北非阿拉伯国家、中东、南欧、北美阿什肯纳兹犹太人群以及已知有欧洲裔影响的南美国家的频率较高。在散发性病例中，频率从无到 35.7%不等，在家族性北非阿拉伯患者中为 42%。仅在一个撒哈拉以南国家发现了一篇论文。确定了方法上的缺陷。
发现估计的频率存在差异，这可能反映了种族差异和方法学差异。我们就参与者的选择方法和家族性帕金森病的定义提出了建议，以提高 LRRK2 突变频率研究的质量。
