Abstract：
Although genetic factors are known to play a role in the pathogenesis of Parkinson\'s disease (PD), true prevalence of familial PD is unknown. We conducted this pilot study to identify genes implicated in familial Parkinson\'s disease among Filipinos.
Eighteen Filipino patients belonging to 11 families with personal and family history of PD underwent thorough evaluation by movement disorders specialists. Samples were analyzed in Juntendo University, Tokyo, Japan. Sanger sequencing of polymerase chain reaction products was performed. Each sample was screened for 23 genes (SNCA, PARK 2, UCHL1, PINK 1, DJ-1, LRRK2, ATP13A2, GIGYF2, HTRA2, PLA266, FBX07, VPS35, EIF461, DNAJC13, CHCHD2, GCH1, MAPT, NR4A2, VPS13c, PSEN1, and GRN).
Out of 18 patients, six harbored Parkinson-related gene mutations. Five individuals from three families were positive for PINK1 c.10140T > C(p.L347P) mutation while one had heterozygous variant PRKN c.136G>T(p.A465) gene mutation. Three families displayed autosomal recessive pattern while one family with PINK1 mutation showed autosomal dominant mode of inheritance. Bradykinesia and tremor were predominant symptoms. Mean age at onset of symptoms was 40.4 years among those with PINK1 mutations.
In this study, we presented the clinical profiles and identified two genetic mutations among a small group of Filipino patients with familial PD. They were congruent with most studies showing these mutations as the most common causes of autosomal recessive early-onset PD. Preliminary data from this pilot study will guide planning for larger scale studies, such as collaborative projects including The Global Parkinson\'s Genetics Program (GP2).
Eighteen Filipino patients belonging to 11 families with personal and family history of PD underwent thorough evaluation by movement disorders specialists. Samples were analyzed in Juntendo University, Tokyo, Japan. Sanger sequencing of polymerase chain reaction products was performed. Each sample was screened for 23 genes (SNCA, PARK 2, UCHL1, PINK 1, DJ-1, LRRK2, ATP13A2, GIGYF2, HTRA2, PLA266, FBX07, VPS35, EIF461, DNAJC13, CHCHD2, GCH1, MAPT, NR4A2, VPS13c, PSEN1, and GRN).
Out of 18 patients, six harbored Parkinson-related gene mutations. Five individuals from three families were positive for PINK1 c.10140T > C(p.L347P) mutation while one had heterozygous variant PRKN c.136G>T(p.A465) gene mutation. Three families displayed autosomal recessive pattern while one family with PINK1 mutation showed autosomal dominant mode of inheritance. Bradykinesia and tremor were predominant symptoms. Mean age at onset of symptoms was 40.4 years among those with PINK1 mutations.
In this study, we presented the clinical profiles and identified two genetic mutations among a small group of Filipino patients with familial PD. They were congruent with most studies showing these mutations as the most common causes of autosomal recessive early-onset PD. Preliminary data from this pilot study will guide planning for larger scale studies, such as collaborative projects including The Global Parkinson\'s Genetics Program (GP2).
摘要：
背景：尽管已知遗传因素在帕金森病（PD）的发病机理中起作用，家族性PD的真实患病率未知。我们进行了这项初步研究，以确定与菲律宾人家族性帕金森氏病有关的基因。
方法：由运动障碍专家对来自11个有PD个人和家族史的家庭的18名菲律宾患者进行了全面评估。在Juntendo大学对样品进行了分析，东京,日本。进行聚合酶链反应产物的Sanger测序。每个样本都筛选了23个基因(SNCA，PARK2,UCHL1,PINK1,DJ-1,LRRK2,ATP13A2,GIGYF2,HTRA2,PLA266,FBX07,VPS35,EIF461,DNAJC13,CHCHD2,GCH1,MAPT,NR4A2,VPS13c,PSEN1和GRN）。
结果：在18名患者中，6个有帕金森相关基因突变.来自三个家庭的五个个体的PINK1阳性c.10140T>C（p。L347P）突变，而一个具有杂合变体PRKNc.136G>T（p。A465)基因突变。三个家庭显示常染色体隐性遗传模式，而一个具有PINK1突变的家庭显示常染色体显性遗传模式。运动迟缓和震颤是主要症状。PINK1突变患者出现症状的平均年龄为40.4岁。
结论：在这项研究中，我们提供了临床资料,并在一小组患有家族性PD的菲律宾患者中发现了两个基因突变.它们与大多数研究一致，这些研究表明这些突变是常染色体隐性隐性早发性PD的最常见原因。这项试点研究的初步数据将指导更大规模研究的规划，如合作项目，包括全球帕金森基因计划（GP2）。
方法：由运动障碍专家对来自11个有PD个人和家族史的家庭的18名菲律宾患者进行了全面评估。
结果：在18名患者中，
结论：在这项研究中，
