Clinical and genetic characterizations of 16q-linked autosomal dominant spinocerebellar ataxia (AD-SCA) and frequency analysis of AD-SCA in the Japanese population
Clinical and genetic characterizations of 16q-linked autosomal dominant spinocerebellar ataxia (AD-SCA) and frequency analysis of AD-SCA in the Japanese population
复制标题
DOI：
10.1002/mds.21443
复制
发表时间：
2007-04-30
影响因子：
8.6
通讯作者：
Onodera, Osamu
中科院分区：
文献类型：
--
作者：
Nozaki, Hiroaki;Ikeuchi, Takeshi;Onodera, Osamu
常染色体显性遗传性脊髓小脑性共济失调(AD-SCA)形成一组临床和遗传异质性的神经退行性疾病。最近研究发现，白藜芦醇-1基因5‘端非转移区的单核苷酸替换与一种16Q染色体连锁的AD-SCA(16Q-SCA)相关。为了进一步了解16Q-SCA患者的临床和遗传学特征，我们分析了686个家系和719个被诊断为进行性共济失调的个体，以进一步了解紫杉醇-1基因C-to-T替换对16Q-SCA患者的临床和遗传学特征的贡献。我们在57个无血缘关系的家系和65个受影响的个体中发现了紫杉醇-1基因的C-to-T替换。16Q-SCA患者的平均发病年龄为59.1岁(范围46-77岁)。共济失调是最常见的首发症状。65岁以上的老年患者偶尔会出现其他伴随的临床特征，包括肌腱反射异常、不自主运动和振动感降低。我们还检查了AD-SCA亚型的频率，考虑了发病年龄的影响。在686个AD-SCA家系中，SCA6和Machado-Joseph病/SCA3是最常见的亚型，其次是齿状核-苍白球萎缩和16Q-SCA。16Q-SCA不是日本AD-SCA的罕见亚型，尤其是在发病年龄超过60岁的患者中。(C)2007年运动无序协会。
Autosomal dominant spinocerebellar ataxias (AD-SCAs) form a clinically and genetically heterogeneous group of neurodegenerative disorders. Recently, a single nucleotide substitution in the 5'-untranstated region of the puratrophin-1 gene was found to be associated with one type of AD-SCA linked to chromosome 16q (16q-SCA). To obtain further insight into the contribution of the C-to-T substitution in the puratrophin-1 gene to the clinical and genetic characteristics of patients with 16q-SCA, we analyzed 686 families with 719 individuals diagnosed with progressive ataxia. We found C-to-T substitution in the puratrophin-1 gene in 57 unrelated families with 65 affected individuals. The mean age at onset in the patients with 16q-SCA was 59.1 (range, 46-77). Ataxia is the most common initial symptom. The elderly patients over 65 occasionally showed other accompanying clinical features including abnormalities in tendon reflexes, involuntary movements, and reduced vibration sense. We also examined the frequency of the AD-SCA subtype, considering the effects of age at onset. In the 686 AD-SCA families, SCA6 and Machado-Joseph disease/ SCA3 are frequent subtypes, followed by dentatorubral-pallidoluysian atrophy and 16q-SCA. 16q-SCA is not a rare subtype of Japanese AD-SCA, particularly in patients with ages at onset over 60. (c) 2007 Movement Disorder Society.