Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism
Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism
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DOI：
10.1038/33416
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发表时间：
1998-04-09
期刊：
影响因子：
64.8
通讯作者：
Shimizu, N
中科院分区：
文献类型：
--
作者：
Kitada, T;Asakawa, S;Shimizu, N
帕金森病是一种常见的神经退行性疾病，具有复杂的临床特征（1）。常染色体隐性青少年帕金森综合征（AR-JP）（2，3）定位于6号染色体长臂（6q25.2-q27），与标记D 6S 305和D 6S 253紧密连锁（参考文献4）;前者在1例日本AR-JP患者中缺失（5）。通过在该微缺失内的定位克隆，我们现在已经分离出具有1，395个碱基对的开放阅读框的2，960个碱基对的互补DNA克隆，其编码465个氨基酸的蛋白质，在氨基末端与泛素具有中等相似性，在羧基末端具有环指基序。该基因跨越500多个酶，具有12个外显子，其中五个（外显子3-7）在患者中缺失，来自三个不相关家族的另外四名AR-JP患者的缺失仅影响外显子4。在许多人体组织中表达但在脑中丰富的4.5-腺苷酸酶转录物，包括黑质，在外显子4缺失患者的脑组织中较短。新发现的基因突变似乎是AR-JP发病机制的原因，因此我们将蛋白质产物命名为“Parkin”。
Parkinson's disease is a common neurodegenerative disease with complex clinical features(1). Autosomal recessive juvenile parkinsonism (AR-JP)(2,3) maps to the long arm of chromosome 6 (6q25.2-q27) and is linked strongly to the markers D6S305 and D6S253 (ref. 4); the former is deleted in one Japanese AR-JP patient(5). By positional cloning within this microdeletion, we have now isolated a complementary DNA clone of 2,960 base pairs with a 1,395-base-pair open reading frame, encoding a protein of 465 amino acids with moderate similarity to ubiquitin at the amino terminus and a RING-finger motif at the carboxy terminus, The gene spans more than 500 kilobases and has 12 exons, five of which (exons 3-7) are deleted in the patient, Four other AR-JP patients from three unrelated families have a deletion affecting exon 4 alone. A 4.5-kilobase transcript that is expressed in many human tissues but is abundant in the brain, including the substantia nigra, is shorter in brain tissue from one of the groups of exon-4-deleted patients. Mutations in the newly identified gene appear to be responsible for the pathogenesis of AR-JP, and we have therefore named the protein product 'Parkin'.