背景:帕金森病(PD)和帕金森病综合征的遗传基础具有挑战性,以及最近关于其遗传途径的发现导致了潜在的基因特异性治疗试验。
方法:我们报告了3例由于磷酸甘油酸激酶1(PGK1)基因的半合子变异引起的X连锁左旋多巴(左旋多巴)反应性帕金森病-癫痫综合征病例。可能的致病变异NM_000291.4(PGK1):c.950G>A;p.(Gly317Asp)被鉴定为半合子状态。
方法:以前只有8例病例将这种表型与PGK1联系起来,PGK1是一种更常见的与溶血性贫血和肌病相关的基因。癫痫的不寻常关联,精神症状,动作震颤,肢体肌张力障碍,认知症状,左旋多巴反应性帕金森病必须引起人们对PGK1突变的注意,特别是因为这个基因在大多数商业遗传性帕金森症组中是不存在的。
结论:本报告旨在揭示一个被忽视的导致遗传性帕金森病综合征的基因。关于PD遗传途径的进一步研究可能会更好地了解其病理生理学,并为新的疾病修饰试验提供可能性。例如SNCA,LRRK2,PRKN,PINK1和DJ-1基因。
BACKGROUND: Genetic underpinnings in Parkinson\'s disease (PD) and parkinsonian syndromes are challenging, and recent discoveries regarding their genetic pathways have led to potential gene-specific treatment trials.
METHODS: We report 3 X-linked levodopa (l-dopa)-responsive parkinsonism-epilepsy syndrome cases due to a hemizygous variant in the phosphoglycerate kinase 1 (PGK1) gene. The likely pathogenic variant NM_000291.4 (PGK1):c.950G > A;p.(Gly317Asp) was identified in a hemizygous state.
METHODS: Only 8 previous cases have linked this phenotype to PGK1, a gene more commonly associated with hemolytic anemia and myopathy. The unusual association of epilepsy, psychiatric symptoms, action tremor, limb dystonia, cognitive symptoms, and l-dopa-responsive parkinsonism must draw attention to PGK1 mutations, especially because this gene is absent from most commercial hereditary parkinsonism panels.
CONCLUSIONS: This report aims to shed light on an overlooked gene that causes hereditary parkinsonian syndromes. Further research regarding genetic pathways in PD may provide a better understanding of its pathophysiology and open possibilities for new disease-modifying trials, such as SNCA, LRRK2, PRKN, PINK1, and DJ-1 genes.