Age dependent penetrance of three different superoxide dismutase 1 (SOD 1) mutations
Age dependent penetrance of three different superoxide dismutase 1 (SOD 1) mutations
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DOI：
10.1080/00207450590914392
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发表时间：
2005-08-01
影响因子：
2.2
通讯作者：
Nicholson, G
中科院分区：
文献类型：
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作者：
Aggarwal, A;Nicholson, G
Cu/Zn超氧化物歧化酶I（SOD 1）突变携带者运动神经元疾病的发病年龄是可变的，从第二个十年的任何时间开始。作者对18世纪80年代以来的家系信息进行了回顾性分析，以确定三种不同SOD 1突变的年龄依赖性突变率：Glu 100 Gly，Ile 113 Thr和Va 1148 Gly。到78岁时，这三种SOD 1突变的症状性MND的患病率大于95%。Va 1148 Gly突变的受影响家庭成员预后最差，平均死亡年龄为46.1岁，而Glu 100 Gly突变为54.2岁，Ile 1 13Thr突变为59.9岁。Kaplan-Meier生存曲线显示，3个SOD 1突变家族合并后的生存期缩短了近10年，所有SOD 1突变携带者的平均死亡年龄为52.6岁，而对照组为62.5岁。与散发性MND相比，SOD 1突变组也导致了更早的死亡，根据自然史研究，这是61.4年。这可能反映了SOD 1突变与疾病进展更快相关，因为发病年龄并不早。这些信息将对SOD 1突变携带者家庭成员的遗传咨询产生重要影响。
The age of onset of motor neuron disease in Cu/Zn superoxide dismutase I (SOD1) mutation carriers are variable, commencing at any time from the second decade. The authors performed a retrospective analysis of family information in pedigrees dating back to the 1780s, to determine the age-dependent penctrance of three different SOD1 mutations: Glu100Gly, Ile113Thr, and Va1148Gly. The penetrance of symptomatic MND in these three SOD1 mutations was greater than 95% by the age of 78. The affected family members with the Va1148Gly mutation had the worst prognosis, with a mean age of death of 46.1 years, compared to 54.2 years for the Glu100Gly mutation and 59.9 years for Ile1 13Thr mutation. Kaplan-Meier survival curves showed that survival of the 3 SOD1 mutation families, when combined, was reduced by nearly 10 years with the mean age of death for all SOD1 mutation carriers being 52.6 years compared to 62.5 years for the control individuals. The SOD1 mutation group also resulted in earlier death compared to sporadic MND, which from natural history studies is 61.4 years. This may reflect that the SOD1 mutation is associated with more progressive and rapid disease, as the age of onset of disease was not earlier. This information would have important implications for genetic counseling of members of individual SOD1 mutation carrier families.