CLINICAL, NEUROPATHOLOGIC, AND GENETIC-STUDIES OF A LARGE SPINOCEREBELLAR ATAXIA TYPE-1 (SCA1) KINDRED - (CAG)(N) EXPANSION AND EARLY PREMONITORY SIGNS AND SYMPTOMS
CLINICAL, NEUROPATHOLOGIC, AND GENETIC-STUDIES OF A LARGE SPINOCEREBELLAR ATAXIA TYPE-1 (SCA1) KINDRED - (CAG)(N) EXPANSION AND EARLY PREMONITORY SIGNS AND SYMPTOMS
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DOI：
10.1212/wnl.45.1.24
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发表时间：
1995-01-01
期刊：
影响因子：
9.9
通讯作者：
ESTIVILL, X
中科院分区：
文献类型：
--
作者：
GENIS, D;MATILLA, T;ESTIVILL, X
我们报告的临床，神经病理学和遗传学研究的一个大的家族（家庭M-ADCA 1）与常染色体显性遗传性脊髓小脑共济失调1型（SCA 1），确定在41名成员，临床数据在22。平均发病年龄为36.3 ± 6.2岁（年龄26 - 52岁），平均病程为15.8 ± 6.5年（范围10 - 28岁），平均死亡年龄为54.1 ± 9.5岁（年龄39 - 72岁）。在许多遗传了突变SCAI基因的临床上未受影响的患者中，先兆体征和症状比通常的发病症状出现得更早。当我们比较第七代和第八代时，我们看到了预期。一个更严重的过程中发生的疾病的后代受影响的男性。神经病理学检查，对三名患者进行，显示SCA 1的常见结果，高尔基体和免疫细胞化学研究表明浦肯野细胞的原发性损害。我们分析了41个家族成员中导致SCA 1表型的CAG重复突变。在19例受试者中有扩增（10例临床受累，7例有早期体征和症状，2例无症状个体），所有受试者均显示杂合性，一个等位基因在41至59个重复之间（SCAI突变），另一个等位基因在6至39个重复之间（正常范围）。对SCA 1突变的“高危”患者的临床分析表明，在完全临床诊断之前，轻微的体征和症状开始，这些先兆表现可以预示SCA 1的全面发展。
We report the clinical, neuropathologic, and genetic studies of a large kindred (family M-ADCA1) with autosomal dominant spinocerebellar ataxia type 1 (SCA1), ascertained in 41 members, with clinical data available in twenty-two. The mean age of onset was 36.3 +/- 6.2 years (ages, 26 to 52), the mean duration of the disease was 15.8 +/- 6.5 years (range, 10 to 28 years), and the mean age at death was 54.1 +/- 9.5 years (ages, 39 to 72). Premonitory signs and symptoms appeared earlier than the usual onset symptoms in many of the clinically unaffected patients who inherited the mutated SCAI gene. Anticipation was present when we compared the seventh and eighth generations. A more severe course of the disease occurred in offspring of affected males. Neuropathologic examination, performed on three patients, showed the usual findings of SCA1; Golgi and immunocytochemistry studies suggested primary damage of the Purkinje cells. We analyzed the CAG-repeat mutation responsible for the SCA1 phenotype in a total of 41 family members. There was expansion in 19 subjects (10 clinically affected, seven with early signs and symptoms, and two asymptomatic individuals), and all showed heterozygosity, with one allele between 41 and 59 repeats (SCAI mutation) and the other in the range of 6 to 39 repeats (normal range). The clinical analysis of ''at risk'' patients with the SCA1 mutation showed that minor signs and symptoms begin before full clinical diagnosis, and these premonitory manifestations can herald full development of SCA1 by years.