Clinicogenetic study of mutations in LRRK2 exon 41 in Parkinson's disease patients from 18 countries
Clinicogenetic study of mutations in LRRK2 exon 41 in Parkinson's disease patients from 18 countries
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DOI：
10.1002/mds.20886
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发表时间：
2006-08-01
影响因子：
8.6
通讯作者：
Hattori, Nobutaka
中科院分区：
文献类型：
--
作者：
Tomiyama, Hiroyuki;Li, Yuanzhe;Hattori, Nobutaka
我们筛选了来自5大洲18个国家的904名帕金森阴性帕金森病（PD）患者（868名先证者）的41号外显子中的LRRK 2突变。我们在LRRK 2外显子41中发现了三个杂合错义突变（新I2012 T、G2019 S和I2020 T）。在868例PD先证者中，我们确定了11例（1.3%），包括2例散发病例和130个常染色体显性PD家系中的8例（6.2%）。外显子41的LRRK 2突变表现出相对常见和全球性分布。在41号外显子的三种突变中，有报道称高加索人G2019 S突变患者具有单奠基者效应。在本研究中，日本G2019 S患者不太可能有来自白人患者的单一创始者。相比之下，I2020 T突变在日本患者中具有单一创始人效应。临床上，LRRK 2突变患者具有典型的特发性PD。值得注意的是，几名患者发展为痴呆和精神病，1名I2020 T患者的心脏I-123-间碘苄基胍（MIBG）心脏/纵隔比率较低，尽管其他I2020 T或G2019 S患者的心脏/纵隔比率并不低。在与LRRK 2突变相关的PD中，包括精神病、痴呆和MIBG比率在内的临床表型也是异质性的，与神经病理学相似。(C)2006年，《社会运动》创刊。
We screened LRRK2 mutations in exon 41 in 904 parkin-negative Parkinson's disease (PD) patients (868 probands) from 18 countries across 5 continents. We found three heterozygous missense (novel I2012T, G2019S, and I2020T) mutations in LRRK2 exon 41. We identified 11 (1.3%) among 868 PD probands, including 2 sporadic cases and 8 (6.2%) of 130 autosomal dominant PD families. The LRRK2 mutations in exon 41 exhibited relatively common and worldwide distribution. Among the three mutations in exon 41, it has been reported that Caucasian patients with G2019S mutation have a single-founder effect. In the present study, Japanese patients with G2019S were unlikely to have a single founder from the Caucasian patients. In contrast, I2020T mutation has a single-founder effect in Japanese patients. Clinically, patients with LRRK2 mutations had typical idiopathic PD. Notably, several patients developed dementia and psychosis, and one with I2020T had low cardiac I-123-metaiodobenzylguanidine (MIBG) heart/mediastinum ratio, although the ratio was not low in other patients with I2020T or G2019S. Clinical phenotypes including psychosis, dementia, and MIBG ratios are also heterogeneous, similar to neuropathology, in PD associated with LRRK2 mutations. (C) 2006 Movement Disorder Society.