Early-onset parkinsonism in a pedigree with phosphoglycerate kinase deficiency and a heterozygous carrier: do PGK-1 mutations contribute to vulnerability to parkinsonism?
Early-onset parkinsonism in a pedigree with phosphoglycerate kinase deficiency and a heterozygous carrier: do PGK-1 mutations contribute to vulnerability to parkinsonism?
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DOI：
10.1038/s41531-017-0014-4
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Mizuno T
中科院分区：
文献类型：
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作者：
Sakaue S;Kasai T;Mizuta I;Suematsu M;Osone S;Azuma Y;Imamura T;Tokuda T;Kanno H;El-Agnaf OMA;Morimoto M;Nakagawa M;Hosoi H;Mizuno T
磷酸甘油酸激酶 1 (PGK-1) 是一种由 PGK-1 编码的糖酵解酶，定位于 X 染色体。 PGK-1 缺乏会因 ATP 再生不足而导致 X 连锁隐性遗传性慢性溶血性贫血、肌病和神经系统疾病。早发性帕金森症偶尔被报道为这种情况的神经系统并发症。然而，PGK-1 缺陷的杂合子携带者被认为没有神经系统症状。在这里，我们报告了一名患有 PGK-1 缺陷的男孩和他的母亲，一名 PGK-1 杂合突变的携带者，两人均患有早发性帕金森病。这名男孩在 9 岁时患上了帕金森症。他的帕金森症对左旋多巴治疗有部分反应。 123l-间碘苄基胍 (MIBG) 摄取正常。他的母亲在红细胞中表现出正常的 PGK-1 活性，但在 36 岁时患上了帕金森病。尽管她正常摄取 MIBG，但她的症状与帕金森病 (PD) 没有区别。未发现 SNCA 的点突变或倍增。此外，LRRK2 和 GBA 的热点没有突变。据我们所知，这份报告首次描述了 PGK-1 缺乏症携带者的帕金森病。有趣的是，PGK-1 位于已确认的 PD 易感位点 PARK12 内。这些观察结果表明 PGK-1 突变赋予 PD 易感性。编码磷酸甘油酸激酶 1 (PGK-1) 的基因突变可能会导致对早发性帕金森病 (PD) 的易感性。 PGK-1 是体内糖分解的关键蛋白质，导致 PGK-1 缺乏的突变会导致 X 连锁代谢紊乱，其特征是红细胞分解、肌肉无力和各种中枢神经系统异常。日本京都府立医科大学的 Takashi Kasai 及其同事描述了一名患有 PGK-1 缺乏症的 9 岁男孩和他 36 岁的母亲的早发性 PD 症状。这是第一份关于 PGK-1 突变无症状携带者发生帕金森病的报告。 PGK-1 基因在 X 染色体上的位置位于已确认的 PD 易感区域（称为 PARK12）内，表明 PGK-1 可能直接导致该疾病。
Phosphoglycerate kinase 1 (PGK-1) is a glycolytic enzyme encoded by PGK-1, which maps to the X chromosome. PGK-1 deficiency causes X-linked recessive hereditary chronic hemolytic anemia, myopathy, and neurological disorders due to insufficient ATP regeneration. Early-onset parkinsonism has occasionally been reported as a neurological complication of this condition. However, heterozygous carriers of PGK-1 deficiency were thought to be neurologically asymptomatic. Here, we report a boy with PGK-1 deficiency and his mother, a carrier of a heterozygous mutation in PGK-1, both of whom presented with early-onset parkinsonism. The boy developed parkinsonism at 9 years of age. His parkinsonism partially responded to levodopa treatment. 123l-metaiodobenzylguanidine (MIBG) uptake was normal. His mother, who exhibited normal PGK-1 activity in erythrocytes, developed parkinsonism at 36 years of age. Her symptoms were undistinguishable from those of Parkinson’s disease (PD), despite her normal uptake of MIBG. Neither a point mutation in nor multiplication of SNCA was found. Additionally, hotspots of LRRK2 and GBA were not mutated. To our knowledge, this report provides the first description of parkinsonism in a carrier of PGK-1 deficiency. Interestingly, PGK-1 is located within the confirmed susceptibility locus for PD known as PARK12. These observations suggest that PGK-1 mutations confer susceptibility to PD. Mutations in the gene encoding phosphoglycerate kinase 1 (PGK-1) may confer susceptibility to early-onset Parkinson’s disease (PD). PGK-1 is a crucial protein for the breakdown of sugar in the body and mutations that cause PGK-1 deficiency lead to an X-linked metabolic disorder characterised by the breakdown of red blood cells, muscle weakness and various central nervous system abnormalities. Takashi Kasai at Kyoto Prefectural University of Medicine, Japan, and colleagues describe early-onset PD symptoms in a 9 year old boy with PGK-1 deficiency and his mother at 36 years of age. This is the first report of parkinsonism developing in an otherwise asymptomatic carrier of a PGK-1 mutation. The location of the PGK-1 gene on the X chromosome is within a confirmed susceptibility region for PD known as PARK12, suggesting that PGK-1 may directly contribute to the disease.