Analysis of Parkinson disease patients from Portugal for mutations in SNCA, PRKN, PINK1 and LRRK2.
Analysis of Parkinson disease patients from Portugal for mutations in SNCA, PRKN, PINK1 and LRRK2.
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DOI：
10.1186/1471-2377-8-1
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发表时间：
2008-01-22
期刊：
影响因子：
2.6
通讯作者：
Singleton A
中科院分区：
文献类型：
--
作者：
Bras J;Guerreiro R;Ribeiro M;Morgadinho A;Januario C;Dias M;Calado A;Semedo C;Oliveira C;Hardy J;Singleton A
基因PRKN和LRRK 2的突变是帕金森病患者中最常见的已知遗传病变。我们以前曾报道过，在葡萄牙人群中LRRK 2 c.6055G > A; p.G2019S突变在欧洲的频率最高。在这里，我们对这些结果进行了随访，在早发性和迟发性家族性葡萄牙帕金森病患者队列中不仅筛选LRRK 2，还筛选PRKN，SNCA和PINK 1。该系列包括从132名患者的连续系列中选择的66名患者。进行此选择是为了仅纳入早发性患者（发病年龄低于50岁）或具有阳性家族史的晚发性患者（至少一名受影响亲属）。对所有基因进行双向测序，此外，对SNCA、PRKN和PINK 1进行基因剂量分析。我们在LRRK 2和PRKN中都发现了突变，而其余的基因没有产生突变。研究的患者中有7例表现出致病性突变，PRKN为纯合性或复合杂合性，LRRK 2为杂合性。突变在葡萄牙帕金森病患者中很常见，这些结果显然不仅对遗传诊断有影响，而且对这些患者的遗传咨询也有影响。
Mutations in the genes PRKN and LRRK2 are the most frequent known genetic lesions among Parkinson's disease patients. We have previously reported that in the Portuguese population the LRRK2 c.6055G > A; p.G2019S mutation has one of the highest frequencies in Europe. Here, we follow up on those results, screening not only LRRK2, but also PRKN, SNCA and PINK1 in a cohort of early-onset and late-onset familial Portuguese Parkinson disease patients. This series comprises 66 patients selected from a consecutive series of 132 patients. This selection was made in order to include only early onset patients (age at onset below 50 years) or late-onset patients with a positive family history (at least one affected relative). All genes were sequenced bi-directionally, and, additionally, SNCA, PRKN and PINK1 were subjected to gene dosage analysis. We found mutations both in LRRK2 and PRKN, while the remaining genes yielded no mutations. Seven of the studied patients showed pathogenic mutations, in homozygosity or compound heterozygosity for PRKN, and heterozygosity for LRRK2. Mutations are common in Portuguese patients with Parkinson's disease, and these results clearly have implications not only for the genetic diagnosis, but also for the genetic counseling of these patients.
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影响因子：
56.9
作者：
Bonifati, V;Rizzu, P;Heutink, P
通讯作者：
Heutink, P
影响因子：
9.9
作者：
Hedrich, K;Djarmati, A;Klein, C
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Klein, C
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11
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HUGHES, AJ;DANIEL, SE;LEES, AJ
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LEES, AJ
影响因子：
56.9
作者：
Singleton, AB;Farrer, M;Gwinn-Hardy, K
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Gwinn-Hardy, K
影响因子：
11.2
作者：
Abou-Sleiman, PM;Healy, DG;Wood, NW
通讯作者：
Wood, NW