目的 对1个遗传性痉挛性截瘫家系进行突变分析与追溯.方法 对2例患者和1名健康个体进行全外显子测序,筛选候选致病突变,并在10名家系成员中通过Sanger测序进行验证.结果 4例患者和3名无症状的年轻个体(25岁以下)携带KIAA0196基因c.1771T＞C突变,而3名无症状的年长个体(40岁以上)未携带该突变.经SIFT、PolyPhen-2和Mutation Taster软件评估,上述变异对于蛋白质功能的影响分别为“有害”,“很可能损伤”和“致病性”.对3名携带者进行随访,一人在采样1年后(26岁)发病,另两人尚无疾病迹象.结论 KIAA0196基因c.1771T＞C位点突变的临床表型具有较大的异质性,该突变可能为遗传性痉挛性截瘫患者常见的致病位点.%Objective To identify pathogenic mutation in a Chinese family affected with hereditary spastic paraplegia (HSP) through genetic testing and a follow-up survey.Methods Whole exome sequencing was performed on DNA samples of two patients and one unaffected member to screen candidate mutations.And Sanger sequencing was used to validate the suspected mutations in all ten family members.Results Four patients and three asymptomatic members (under 25 years old) carried the c.1771T＞C mutation of the KIAA0196,while the other three asymptomatic members (over 40 years old) did not carry the mutation.This mutation was predicted to be "affect protein function","probably damaging" and "disease causing" by SIFT,PolyPhen-2 and Mutation Taster,respectively.Three asymptomatic carriers were followed up and one of them developed into HSP one year later,while the other two had no signs of the disease yet.Conclusion The clinical phenotype of the c.1771T ＞ C mutation of KIAA0196 has a considerable heterogeneity and this mutation may be a common pathogenic site of KIAA0196 mutation in Chinese patients with hereditary spastic paraplegia.
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