University of Miami, Miller School of Medicine, John P. Hussman Institute for Human Genomics Miami, FL 33136, USA.
Hum Mutat. 2010 Oct;31(10):E1767-71. doi: 10.1002/humu.21351.
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.
酪氨酸羟化酶（TH）酶是多巴胺生物合成中的限速酶。已知 TH 基因的两个等位基因突变会导致多巴胺相关表型，包括肌张力障碍和婴儿性帕金森病。然而，TH 基因单等位基因突变是否会改变成年帕金森病（PD）的易感性尚不清楚。我们报道了一例成年 PD 患者 TH 基因全部缺失。该缺失首先通过使用 Illumina Infinium BeadChips 的全基因组关联研究中的拷贝数变异（CNV）分析来鉴定。在筛选了 635 例病例和 642 例对照后，该缺失在一例 PD 病例中发现，但在任何对照中均未发现。该缺失通过多种定量 PCR（qPCR）检测得到确认。患者的 TH 基因的一份拷贝中没有其他外显子单核苷酸变异。该患者发病年龄为 54 岁，无肌张力障碍证据，对 L-DOPA 有反应。该病例支持 TH 基因在 PD 发病机制中的重要性，并引起更多关注候选基因中的罕见变异是帕金森病的一个危险因素。
