Parkin deletions in a family with adult-onset, tremor-dominant parkinsonism:: Expanding the phenotype
Parkin deletions in a family with adult-onset, tremor-dominant parkinsonism:: Expanding the phenotype
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DOI：
10.1002/1531-8249(200007)48:1
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发表时间：
2000-07-01
影响因子：
11.2
通讯作者：
Ozelius, LJ
中科院分区：
文献类型：
--
作者：
Klein, C;Pramstaller, PP;Ozelius, LJ
常染色体隐性遗传性帕金森综合征（PARK）的一个基因？（parkin），最近在染色体6q上被鉴定，并且在日本和欧洲家庭中显示出突变，大多数具有早发性帕金森症。在这里，我们提出了一个大的家系从南蒂罗尔（北方意大利的一个地区）与成人发病，临床典型震颤显性帕金森症的明显常染色体显性遗传。单倍型分析排除了与染色体2p、4p和4q区域的连锁，这些区域含有与常染色体显性帕金森综合征相关的基因，但涉及染色体6q上的parkin位点。复合杂合缺失帕金基因（一个大的和一个截断）被确定在4个受影响的男性同胞。这些患者在临床上与大多数特发性帕金森病患者难以区分。他们都没有表现出任何的临床特征，在先前报告的帕金突变，包括昼夜波动，睡眠，足部肌张力障碍，反射亢进，以及早期易感左旋多巴诱导的运动障碍患者中描述。两个受影响的女性个体携带一个（截短）的两个缺失的杂合状态与一个明显正常的等位基因。我们的结论是，与parkin基因突变相关的表型谱比以前报道的更广泛，这表明该基因可能是更频繁的晚发型典型帕金森病的病因学中的重要。
A gene for autosomal recessive parkinsonism, PARK;? (parkin), has recently been identified on chromosome 6q and shown to be mutated in Japanese and European families, mostly with early-onset parkinsonism. Here we present a large pedigree from South Tyrol (a region of northern Italy) with adult-onset, clinically typical tremor-dominant parkinsonism of apparently autosomal dominant inheritance. Haplotype analysis excluded linkage to the chromosome 2p, 4p, and 4q regions that harbor genes associated with autosomal dominant parkinsonism, but implicated the parkin locus on chromosome 6q. Compound heterozygous deletions in the parkin gene (one large and one truncating) were identified in 4 affected male siblings. The patients were clinically indistinguishable from most patients with idiopathic Parkinson's disease. None of them displayed any of the clinical hallmarks described in patients with previously reported parkin mutations, including diurnal fluctuations, benefit from sleep, foot dystonia, hyperreflexia, and early susceptibility to levodopa-induced dyskinesias. Two affected female individuals carried one (truncating) of the two deletions in a heterozygous state with an apparently normal allele. We conclude that the phenotypic spectrum associated with mutations in the parkin gene is broader than previously reported, suggesting that this gene may be important in the etiology of the more frequent late-onset typical Parkinson's disease.