A Rare Novel Deletion of the Tyrosine Hydroxylase Gene in Parkinson Disease
A Rare Novel Deletion of the Tyrosine Hydroxylase Gene in Parkinson Disease
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DOI：
10.1002/humu.21351
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发表时间：
2010-10-01
期刊：
影响因子：
3.9
通讯作者：
Wang, Liyong
中科院分区：
文献类型：
--
作者：
Bademci, Gueney;Edwards, Todd L.;Wang, Liyong
酪氨酸羟化酶（TH）是多巴胺生物合成中的限速酶。 TH 基因的两个等位基因的错义突变已知会导致多巴胺相关表型，包括肌张力障碍和婴儿帕金森症。然而，尚不清楚 TH 的单个等位基因突变是否会改变成人帕金森病 (PD) 的易感性。我们报道了一名患有帕金森病的成人中整个 TH 基因的新缺失。该缺失首先是在使用 Illumina Infinium BeadChips 的全基因组关联研究中通过拷贝数变异 (CNV) 分析发现的。在对 635 例病例和 642 例对照进行筛查后，在 1 例 PD 病例中发现了该缺失，但在任何对照中均未发现该缺失。通过多重定量 PCR (qPCR) 测定证实了缺失。患者的一份TH基因中没有额外的外显子单核苷酸变异。该患者的发病年龄为 54 岁，没有肌张力障碍的证据，并且对左旋多巴有反应。该病例支持了 TH 基因在帕金森病发病机制中的重要性，并引起了人们对作为帕金森病危险因素的候选基因中罕见变异的更多关注。 (C) 2010 Wiley-Liss, Inc.
Tyrosine hydroxylase (TH) enzyme is a rate limiting enzyme in dopamine biosynthesis. Missense mutation in both alleles of the TH gene is known to cause dopamine-related phenotypes, including dystonia and infantile Parkinsonism. However, it is not clear if single allele mutation in TH modifies the susceptibility to the adult form of Parkinson disease (PD). We reported a novel deletion of entire TH gene in an adult with PD. The deletion was first identified by copy number variation (CNV) analysis in a genome-wide association study using Illumina Infinium BeadChips. After screening 635 cases and 642 controls, the deletion was found in one PD case but not in any control. The deletion was confirmed by multiple quantitative PCR (qPCR) assays. There is no additional exonic single nucleotide variant in the one copy of TH gene of the patient. The patient has an age-at-onset of 54 years, no evidence for dystonia, and was responsive to L-DOPA. This case supports the importance of the TH gene in PD pathogenesis and raises more attention to rare variants in candidate genes being a risk factor for Parkinson disease. (C) 2010 Wiley-Liss, Inc.