目的 通过对43个中国家族性肌萎缩侧索硬化(FALS)家系先证者进行铜、锌超氧化物歧化酶(SOD)1基因突变检测,分析其与临床表型的关系,探讨中国FAIS患者SOD1基因的突变分布谱及其与临床表型之间的关联性.方法 采集2008-2011年确诊的43个FALS家系的临床资料.利用PCR技术和直接测序方法,检测先证者SOD1基因突变,进一步与临床表型做关联分析.结果 43个FALS家系均呈常染色体显性遗传,先证者男女比例为1∶0.6,起病年龄(48.1±11.8)岁,上肢起病23例,占53.5％,下肢起病18例,占41.9％,延髓部起病2例,占4.6％.在10例先证者中共发现9种SOD1突变类型,其中2种为未报道的新突变.9种突变类型中8种为错义突变,1种为缺失突变.SOD1基因突变总检出率为23.3％.结论 中国FALS患者SOD1基因突变类型由原来的11种增加到19种.具有SOD1突变的FALS患者以下运动神经元损害为主.大多数SOD1突变的临床表型在不同的家系甚至同一家系中变异均较大.%Objective To identify the patterns of population distribution and the relationship of copper-zinc superoxide dismutase 1 (SOD1) mutations and clinical phenotypes in Chinese patients with familial amyotrophic lateral sclerosis (FALS).Methods The clinical data of 43 FALS families from 2008 to 2011 were collected,SOD1 gene mutations in the probands were screened with PCR and direct sequencing,and the correlations of genotype-phenotype were analyzed.Results All 43 FALS families were autosomal dominant inheritance.The male to female ratio for probands was 1∶0.6,and the average onset age was (48.1 ± 11.8) years.Upper limb onset accounted for 53.5％,lower limb onset 41.9％,and bulbar onset 4.6％.Nine mutation types including 8 missense mutations and 1 deletion mutation were detected in 10 probands.The detection rate of SOD1 mutations in this cohort was 23.3％.Conclusions The study reported the correlations of genotype-phenotype of SOD1 in a larger group of Chinese FALS patients.Two novel mutations were found including one deletion mutation.SOD1 mutations increased from 11 to 19 in Chinese FALS.For SOD1 patients,lower motor neuron signs usually predominated.Most clinical phenotypes of one mutation varied greatly in different families even in the same family.
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