PINK1 heterozygous rare variants: Prevalence, significance and phenotypic spectrum
PINK1 heterozygous rare variants: Prevalence, significance and phenotypic spectrum
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DOI：
10.1002/humu.20719
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发表时间：
2008-04-01
期刊：
影响因子：
3.9
通讯作者：
Valente, Enza Maria
中科院分区：
文献类型：
--
作者：
Marongiu, Roberta;Ferraris, Alessandro;Valente, Enza Maria
PINK 1基因以及其他基因中的杂合罕见变异导致常染色体隐性帕金森综合征，在患者和健康对照中都有报道。它们的致病意义尚不确定，但已被认为是发展帕金森病（PD）的危险因素。少数评估病例和对照中PINK 1杂合子频率的大型研究产生了有争议的结果，表型谱在很大程度上是未知的。我们回顾性分析了超过1100例所有发病年龄的散发性和家族性患者以及400例对照中PINK 1杂合罕见变异的发生情况。20例患者和6例对照为杂合子，两组的频率（1.8% vs. 1.5%）无显著差异。杂合子的临床特征与野生型患者的临床特征无明显区别，平均发病时间比两种仿制品携带者晚10年，但疾病进展更差。一项荟萃分析表明，在PINK 1杂合子中，PD风险仅略有增加，比值比为1.62，不显著。这些发现表明，PINK 1杂合罕见变异在PD的多因素模型中仅起次要的易感作用。因此，它们的意义应该与纯合子/复合杂合子的启始区别开来，后者导致以孟德尔方式遗传的帕金森症。(c)2008威利利斯公司
Heterozygous rare variants in the PINK1 gene, as well as in other genes Causing autosomal recessive parkinsonism, have been reported both in patients and healthy controls. Their pathogenic significance is uncertain, but they have been suggested to represent risk factors to develop Parkinson disease (PD). The few large Studies that assessed the frequency of PINK1 heterozygotes in cases and controls yielded controversial results, and the phenotypic spectrum is largely unknown. We retrospectively analyzed the occurrence of PINK1 heterozygous rare variants in over 1100 sporadic and familial patients of all onset ages and in 400 controls. Twenty patients and 6 controls were heterozygous, with frequencies (1.8% vs. 1.5%) not significantly different in the two groups. Clinical features of heterozygotes were indistinguishable to those of wild-type patients, with mean disease onset 10 years later than in carriers of two imitations but Worse disease progression. A meta-analysis indicated that, in PINK1 heterozygotes, the PD risk is only slightly increased with a non significant odds ratio of 1.62. These findings Suggest that PINK1 heterozygous rare variants play only a minor susceptibility role in the context of a multifactorial model of PD. Hence, their significance Should be kept distinct from that Of homozygous/compound heterozygous Initiations, that cause parkinsonism inherited in a mendelian fashion. (c) 2008 Wiley-Liss, Inc.