Park6‐linked parkinsonism occurs in several european families
Park6‐linked parkinsonism occurs in several european families
复制标题
Park6相关帕金森病发生在几个欧洲家庭中
作者：
E. Valente;F. Brancati;A. Ferraris;E. Graham;M. Davis;M. Breteler;T. Gasser;V. Bonifati;A. Bentivoglio;G. De Michele;A. Dürr;P. Cortelli;Dietmar Wassilowsky;B. Harhangi;N. Rawal;V. Caputo;A. Filla;G. Meco;B. Oostra;A. Brice;A. Albanese;B. Dallapiccola;N. Wood
6q25.2-27上的Parkin基因负责约50%的常染色体隐性青少年帕金森综合征和不到20%的散发性早发性病例。我们最近在一个来自西西里的大家族中定位了一个位于染色体1 p35-p36上的早发性帕金森综合征（PARK 6）的新位点。我们现在确认了来自四个不同欧洲国家的另外八个帕金森阴性常染色体隐性青少年帕金森综合征家族与PARK 6的联系。标记D1 S478的最大累积成对LOD评分为5.39。多点连锁分析得出标记D1 S478的最高累积LOD得分为6.29。单倍型的建设和确定的最小区域的纯合性在一个血缘家庭的候选人之间的间隔减少到9 cM的区域标记D1 S483和D1 S2674。没有共同的单倍型可以检测到，排除了共同的创始人效应。这些家族与欧洲帕金阳性病例报告的表型有一些共同的临床特征，发病年龄范围广（最高68岁），进展缓慢。然而，在PARK 6连锁家族中未观察到常染色体隐性遗传青少年帕金森综合征的典型特征，包括发作时的肌张力障碍和睡眠益处，因此使晚发型病例的临床表现与特发性帕金森病难以区分。PARK 6似乎是欧洲Parkin阴性患者中早发性帕金森综合征的重要位点。
The Parkin gene on 6q25.2–27 is responsible for about 50% of autosomal recessive juvenile parkinsonism and less than 20% of sporadic early‐onset cases. We recently mapped a novel locus for early‐onset parkinsonism (PARK6) on chromosome 1p35–p36 in a large family from Sicily. We now confirm linkage to PARK6 in eight additional families with Parkin‐negative autosomal recessive juvenile parkinsonism from four different European countries. The maximum cumulative pairwise LOD score was 5.39 for marker D1S478. Multipoint linkage analysis gave the highest cumulative LOD score of 6.29 for marker D1S478. Haplotype construction and determination of the smallest region of homozygosity in one consanguineous family has reduced the candidate interval to a 9cM region between markers D1S483 and D1S2674. No common haplotype could be detected, excluding a common founder effect. These families share some clinical features with the phenotype reported for European Parkin‐positive cases, with a wide range of ages at onset (up to 68 yrs) and slow progression. However, features typical of autosomal recessive juvenile parkinsonism, including dystonia at onset and sleep benefit, were not observed in PARK6‐linked families, thus making the clinical presentation of late‐onset cases indistinguishable from idiopathic Parkinson's disease. PARK6 appears to be an important locus for early‐onset parkinsonism in European Parkin‐negative patients.
影响因子：
9.8
作者：
E. Sobel;K. Lange
通讯作者：
E. Sobel;K. Lange