Phenotypic heterogeneity in motor neuron disease patients with CuZn-superoxide dismutase mutations in Scandinavia
Phenotypic heterogeneity in motor neuron disease patients with CuZn-superoxide dismutase mutations in Scandinavia
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DOI：
10.1093/brain/120.10.1723
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发表时间：
1997-10-01
期刊：
影响因子：
14.5
通讯作者：
Marklund, SL
中科院分区：
文献类型：
--
作者：
Andersen, PM;Nilsson, P;Marklund, SL
对来自斯堪的纳维亚运动神经元病患者的451份血液样本进行了铜锌超氧化物歧化酶基因突变分析。在427例肌萎缩侧索硬化症(ALS)患者中，41例(9.6%)被发现存在疾病相关突变，其中14例明显为散发病例。在51个家族性肌萎缩侧索硬化症家系中有12个发现了突变。发现的五种不同的突变(Ala4Val，Val14Gly，Asp76Tyr；Asp90Ala，Gly127insTGGG)具有不同的遗传特征，与非常不同的表型有关，从只有下运动神经元体征的快速进展疾病到非常缓慢进展的疾病，患者的上下运动神经元系统都显示出不同的发病部位，尽管进行性球麻痹形式的疾病似乎是罕见的铜锌超氧化物歧化酶突变的患者。在不同突变的患者中，运动体征和症状的进展遵循相同的基本模式。携带铜锌超氧化物歧化酶突变的患者经常出现运动外系统症状。结果表明，铜锌超氧化物歧化酶基因突变的患者构成一个疾病实体。Val14Gly和Asp76Tyr突变以前从未报道过，后者是在CuZn-超氧化物歧化酶基因外显子3发现的第一个突变。
Four-hundred and fifty-one blood samples from Scandinavian patients with motor neuron disease were analysed for mutations in the CuZn-superoxide dismutase gene. Forty-one (9.6%) of the 427 patients with the amyotrophic lateral sclerosis (ALS) form of the disease were found to have a disease-associated mutation, and 14 of these patients were apparently sporadic cases. A mutation was found in 12 of the 51 families with recognized familial ALS. The five different mutations found (Ala4Val, Val14Gly, Asp76Tyr; Asp90Ala, Gly127insTGGG) have different genetic characteristics and are associated with very variable phenotypes spanning from rapidly progressing disease with only lower motor neuron signs to very slowly progressing disease with both the upper and lower motor neuron systems affected The patients showed different sites of onset, though the progressive bulbar palsy form of the disease appears to be rare among patients with a CuZn-superoxide dismutase mutation. The progression of motor signs and symptoms followed the same basic pattern in patients with different mutations. Extra-motor system symptoms were frequent among patients with a CuZn-superoxide dismutase mutation. The results suggest that patients with mutations in the CuZn-superoxide dismutase gene constitute one disease entity. The Val14Gly and Asp76Tyr mutations have not been reported before, and the latter is the first mutation to be found in exon 3 of the CuZn-superoxide oxide dismutase gene.