Camargos Sarah Teixeira, Dornas Leonardo Oliveira, Momeni Parastoo, Lees Andrew, Hardy John, Singleton Andrew, Cardoso Francisco
Movement Disorders Group, Neurology Service, Department of Internal Medicine, Federal University of Minas Gerais, Minas Gerais, Brazil.
Mov Disord. 2009 Apr 15;24(5):662-6. doi: 10.1002/mds.22365.
The aim of the study was to evaluate the frequency and to perform phenotypic and genotypic characterization of familial Parkinsonism and early onset Parkinson's disease (EOPD) in a Brazilian movement disorder unit. We performed a standardized clinical assessment of patients followed by sequencing of PRKN, PINK1 in EOPD cases and SNCA, LRRK2 in familial Parkinsonism individuals. During the period of study (January through December, 2006), we examined 575 consecutive patients of whom 226 (39.3%) met the diagnosis of Parkinsonism and idiopathic Parkinson's disease (IPD) was diagnosed in 202 of the latter. Of the IPD cases, 45 (22.3%) had EOPD. The age at onset in the EOPD cases (n = 45) was 34.8 +/- 5.4 years (mean +/- standard deviation). The age at onset in the familial late-onset PD patients (n = 8) was 52.3 +/- 12.2 years. In the early onset cases, we identified five known mutations in PRKN, two single heterozygous and three compound heterozygous (P153R, T240M, 255Adel, W54R, V3I); in addition, we identified one novel mutation in PINK1 (homozygous deletion of exon 7). In the familial cases (late onset), 1 patient had a novel LRRK2 variant, Q923H, but no SNCA mutations were identified. We have demonstrated that EOPD accounts for a high frequency of IPD cases in our tertiary referral center. PRKN was the most commonly mutated gene, but we also identified a novel mutation in PINK1 and a novel variant in LRRK2.
本研究的目的是评估巴西一家运动障碍治疗中心家族性帕金森综合征和早发性帕金森病（EOPD）的发病频率，并进行表型和基因型特征分析。我们对患者进行了标准化临床评估，随后对EOPD病例中的PRKN、PINK1基因以及家族性帕金森综合征患者中的SNCA、LRRK2基因进行测序。在研究期间（2006年1月至12月），我们检查了575例连续患者，其中226例（39.3%）符合帕金森综合征诊断，后者中有202例被诊断为特发性帕金森病（IPD）。在IPD病例中，45例（22.3%）为EOPD。EOPD病例（n = 45）的发病年龄为34.8±5.4岁（平均值±标准差）。家族性晚发性帕金森病患者（n = 8）的发病年龄为52.3±12.2岁。在早发性病例中，我们在PRKN基因中鉴定出5个已知突变，2个单杂合突变和3个复合杂合突变（P153R、T240M、255Adel、W54R、V3I）；此外，我们在PINK1基因中鉴定出1个新突变（外显子7纯合缺失）。在家族性病例（晚发性）中，1例患者有LRRK2基因新变异Q923H，但未鉴定出SNCA基因突变。我们已经证明，在我们的三级转诊中心，EOPD在IPD病例中占很高比例。PRKN是最常发生突变的基因，但我们也在PINK1基因中鉴定出1个新突变和LRRK2基因中的1个新变异。
