Department of Neurogenetics and Molecular Biology, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Insurgentes Sur 3877, Col. La Fama, Tlalpan, 14269 Mexico City, D.F., Mexico.
Neurosci Lett. 2010 Nov 19;485(2):79-82. doi: 10.1016/j.neulet.2010.08.029. Epub 2010 Aug 18.
Mutations in leucine-rich repeat kinase 2 gene (LRRK2) account for as much as 5-6% of familial Parkinson's disease (PD) and 1-2% of sporadic PD. These mutations represent the most frequent cause of autosomal dominant PD, particularly in certain ethnic groups. In this first report concerning LRRK2 mutations in Mexican-mestizos, we screened 319 consecutive PD patients (186 males; 133 females; mean age at onset: 52.4 years) for LRRK2 mutations in exons 31 and 41 and for the mutation in exon 35, which produces the Y1699C substitution. Three (0.94%) patients, two with sporadic PD and one with familial PD (disease mean age at onset, 53.3 years), were heterozygous for LRRK2 mutations. Of these three, two patients had one of two different mutations in exon 31 (R1441G and R1441H, respectively); the other patient carried the G2019S mutation in exon 41. The Y1699C mutation was absent from this PD sample. Four additional subjects, unaffected relatives of one PD patient with a mutation in LRRK2, were subsequently genetically tested. None of the three LRRK2 mutations identified was present in 200 neurologically healthy Mexican control individuals. These findings have important implications for molecular testing of LRRK2 mutations in Mexican PD patients.
LRRK2 基因突变占家族性帕金森病 (PD) 的 5-6%,占散发性 PD 的 1-2%。这些突变代表了最常见的常染色体显性 PD 原因,尤其是在某些种族群体中。在关于墨西哥裔人群中 LRRK2 突变的首次报告中,我们筛选了 319 名连续的 PD 患者(186 名男性;133 名女性;发病年龄平均:52.4 岁),以寻找外显子 31 和 41 中的 LRRK2 突变以及导致 Y1699C 取代的外显子 35 中的突变。有 3 名(0.94%)患者,2 名为散发性 PD,1 名为家族性 PD(疾病发病年龄平均:53.3 岁),为 LRRK2 突变的杂合子。其中 2 名患者在外显子 31 中具有两种不同的突变之一(分别为 R1441G 和 R1441H);另一名患者在外显子 41 中携带 G2019S 突变。在这个 PD 样本中未发现 Y1699C 突变。随后对一名患有 LRRK2 突变的 PD 患者的 4 名未受影响的亲属进行了基因检测。在 200 名神经健康的墨西哥对照个体中,未发现这 3 种 LRRK2 突变中的任何一种。这些发现对在墨西哥 PD 患者中进行 LRRK2 突变的分子检测具有重要意义。