Multiplex families with multiple system atrophy
Multiplex families with multiple system atrophy
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DOI：
10.1001/archneur.64.4.545
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发表时间：
2007-04-01
影响因子：
--
通讯作者：
Tsuji, Shoji
中科院分区：
文献类型：
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作者：
Hara, Kenju;Momose, Yoshio;Tsuji, Shoji
背景资料：多系统萎缩症（MSA）是一种散发性疾病，无遗传模式，目的：描述4个多发性MSA家系的临床特征，包括临床遗传学方面。设定：患者：来自4个家族的8例帕金森综合征、小脑性共济失调和自主神经功能衰竭患者，发病年龄为58 - 72岁。两个兄弟姐妹在每个家庭中受到影响，这些conditions.Main结果措施：临床评价进行了根据标准Gilman等。三核苷酸重复扩增的脊髓小脑共济失调（SCA）系列和齿状核红核苍白球路易体萎缩（DRPLA）的责任基因进行了评价聚合酶链反应。结果：4个家系中有1个为近亲结婚。在8例患者中，1例明确MSA，5例可能MSA，2例可能MSA。最常见的表型为MSA伴帕金森综合征，见于5例患者。6例患者在脑磁共振成像上显示脑桥萎缩，在后外侧壳核边缘有十字征或裂隙样信号改变或两者兼而有之。遗传性共济失调，包括SCA 1（共济失调蛋白1，ATXN 1）、SCA 2（ATXN 2）、Machado-Joseph病/SCA 3（ATXN 1）、SCA 6（ATXN 1）、SCA 7（ATXN 7）、SCA 12（蛋白磷酸酶2，调节亚基B，β亚型; PP 2 R2 B），SCA 17（TATA盒结合蛋白，TBP）和DRPLA（atrophin 1; ATN 1），并且没有发现α-突触核蛋白基因的突变。在这些多重家庭的调查结果表明，存在家族性MSA与常染色体隐性遗传和遗传易感性MSA。针对家族性MSA的分子遗传学研究有望为MSA的发病机制提供线索。
Background: Multiple system atrophy (MSA) has been considered a sporadic disease, without patterns of inheritance.Objective: To describe the clinical features of 4 multiplex families with MSA, including clinical genetic aspects.Design: Clinical and genetic study. Setting: Four departments of neurology in Japan.Patients: Eight patients in 4 families with parkinsonism, cerebellar ataxia, and autonomic failure with age at onset ranging from 58 to 72 years. Two siblings in each family were affected with these conditions.Main Outcome Measures: Clinical evaluation was performed according to criteria by Gilman et al. Trinucleotide repeat expansion in the responsible genes for the spinocerebellar ataxia (SCA) series and for dentatorubral-pallidoluysian atrophy (DRPLA) was evaluated by polymerase chain reaction. Direct sequence analysis of coding regions in the alpha-synuclein gene was performed.Results: Consanguineous marriage was observed in 1 of 4 families. Among 8 patients, 1 had definite MSA, 5 had probable MSA, and 2 had possible MSA. The most frequent phenotype was MSA with predominant parkinsonism, observed in 5 patients. Six patients showed pontine atrophy with cross sign or slitlike signal change at the posterolateral putaminal margin or both on brain magnetic resonance imaging. Possibilities of hereditary ataxias, including SCA1 (ataxin 1, ATXN1), SCA2 (ATXN2), Machado-Joseph disease/SCA3 (ATXN1), SCA6 (ATXN1), SCA7 (ATXN7), SCA12 (protein phosphatase 2, regulatory subunit B, beta isoform; PP2R2B), SCA17 (TATA box binding protein, TBP) and DRPLA (atrophin 1; ATN1), were excluded, and no mutations in the alpha-synuclein gene were found.Conclusions: Findings in these multiplex families suggest the presence of familial MSA with autosomal recessive inheritance and a genetic predisposition to MSA. Molecular genetic approaches focusing on familial MSA are expected to provide clues to the pathogenesis of MSA.