Alpha-synuclein multiplications with parkinsonism, dementia or progressive myoclonus?
Alpha-synuclein multiplications with parkinsonism, dementia or progressive myoclonus?
复制标题
DOI：
10.1016/j.parkreldis.2008.08.002
复制
发表时间：
2009-06-01
影响因子：
4.1
通讯作者：
Nilsson, Christer
中科院分区：
文献类型：
--
作者：
Puschmann, Andreas;Wszolek, Zbigniew K.;Nilsson, Christer
据报道，瑞典南部“Lister 家族”的帕金森病患者存在 α-突触核蛋白 (SNCA) 基因的重复和三重复。进一步的家谱研究现在表明，这些人是赫尔曼·伦德堡 (Herman Lundborg) 在 1901 年至 1913 年所描述的一个大家族的后裔。在扩大的家系中，共有 25 名个体患有常染色体显性遗传模式的帕金森病。遗传性痴呆症以及历史上的早发性痴呆症也曾在其他家庭成员中被描述过。此外，Lundborg 在同一谱系中描述了一种常染色体隐性遗传的儿科疾病，伴有夜间强直阵挛发作、随后进行性肌阵挛、惊吓反应、震颤和肌肉强直。该实体后来被命名为 Unverricht-Lundborg 病 (ULD) 或进行性肌阵挛癫痫 I 型 (EPM1)。然而，Lundborg 基于该家族的 17 名患者对这种疾病的临床描述与 EPM1 的现代定义不同，后者依赖于半胱氨酸蛋白酶抑制剂 B (CSTB) 基因突变的患者。我们假设以前的儿科疾病以及帕金森病和痴呆表型与 α-突触核蛋白 (SNCA) 基因的重复、三倍和可能的高阶倍增有关。这一假设得到了谱系中受影响家庭成员的分布以及最近获得的家谱信息的支持。 (C) 2008 Elsevier Ltd. 保留所有权利。
Duplications and triplications of the alpha-synuclein (SNCA) gene have been reported in Parkinson's disease patients belonging to the Southern Swedish "Lister family". Further genealogical research has now shown that these individuals are descended from a large kindred characterized by Herman Lundborg in 1901-1913. In the expanded pedigree, a total of 25 individuals had Parkinson's disease with an autosomal dominant pattern of inheritance. Hereditary dementia, and, historically, dementia praecox have been described in other family members. Furthermore, an autosomal recessively inherited pediatric disease with nocturnal tonic-clonic fits, subsequent progressive myoclonus, startle reactions, tremor and muscle rigidity was described by Lundborg in the same pedigree. The entity was later designated Unverricht-Lundborg disease (ULD) or progressive myoclonus epilepsy type I (EPM1). However, Lundborg's clinical description of this disease, based on 17 patients within this kindred, differs from the modern definition of EPM1, which relies on patients with a mutation in the cystatin B (CSTB) gene. We hypothesize that the former pediatric disease, as well as the parkinsonism, and dementia phenotypes, are associated with duplications, triplications and possibly higher-order multiplications of the alpha-synuclein (SNCA) gene. This hypothesis is supported by the distribution of afflicted family members within the pedigree and by recently obtained genealogical information. (C) 2008 Elsevier Ltd. All rights reserved.