Novel mutation in ATP13A2 widens the spectrum of Kufor-Rakeb syndrome (PARK9)
Novel mutation in ATP13A2 widens the spectrum of Kufor-Rakeb syndrome (PARK9)
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DOI：
10.1111/j.1399-0004.2011.01745.x
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发表时间：
2012-09-01
影响因子：
3.5
通讯作者：
Nielsen, J. E.
中科院分区：
文献类型：
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作者：
Eiberg, H.;Hansen, L.;Nielsen, J. E.
Kufor-Rakeb综合征（KRS）是一种罕见的常染色体隐性遗传青少年帕金森综合征，由ATP 13 A2突变引起。我们描述了一个格陵兰因纽特人的近亲家庭，纯合子的一个新的移码突变在外显子22的ATP 13 A2（c.2473C>AA，p.Leu825AsnfsX32）的6例患者。最新报告的疾病发病年龄为10至29岁，在具有认知/精神特征的广泛的锥体外系综合征中，临床特征高度可变。在两名患者中观察到共济失调，在一名患者中观察到轴索神经病变，这些特征以前与KRS无关。多巴胺转运蛋白扫描显示对称，严重减少摄取纹状体中的两名患者。磁共振成像没有萎缩的一名患者，尽管疾病的持续时间为17年，和大脑和小脑萎缩后，在另一名患者的疾病持续时间为4年。讨论了ATP 13 A2突变的分子致病机制。观察到突变体转录物不被无义介导的RNA衰变降解，并且来自该家族的8个杂合携带者中没有一个具有KRS症状，这表明突变体蛋白不干扰和破坏野生型ATP 13 A2蛋白的功能。
Kufor-Rakeb syndrome (KRS) is a rare autosomal recessive inherited juvenile parkinsonian syndrome caused by mutations in ATP13A2. We describe six patients from a consanguineous Greenlandic Inuit family, homozygous for a novel frame-shift mutation in exon 22 of ATP13A2 (c.2473C>AA, p.Leu825AsnfsX32). Disease onset varied from 10 to 29 years of age, the latest reported, and the clinical features were highly variable within a wide spectrum of an extrapyramidal-pyramidal syndrome with cognitive/psychiatric features. Ataxia was seen in two patients and axonal neuropathy in one, features not previously related to KRS. Dopamine transporter scans showed symmetrical, severely reduced uptake in striatum in two patients. Magnetic resonance imaging was without atrophy in one patient despite disease duration of 17 years, and cerebral and cerebellar atrophy was seen in another patient after 4 years of disease duration. The molecular pathogenic mechanisms of ATP13A2 mutations are discussed. The observation that the mutant transcript is not degraded by nonsense-mediated RNA decay and the fact that none of the eight heterozygous carriers from the family have KRS symptoms suggest that the mutant protein does not interfere and destroy the function of the wild-type ATP13A2 protein.