早发性家族性阿尔茨海默病家系的临床表型及基因突变分析  

Clinical Phenotype and Gene Mutation Analysis of a Family with Early-Onset Familial Alzheimer′s Disease

作　　者：李燕坤 庄顺芝 何菲[3] 陈礼锟 张停亭 崔理立 李才明[2] LI Yan-kun;ZHUANG Shun-zhi;HE Fei;CHEN Li-kun;ZHANG Ting-ting;CUI Li-li;LI Cai-ming(Guangdong Medical University,Zhanjiang 524000,China;Department of Neurology,Huizhou First People′s Hospital,Huizhou 516003,China;Department of Genetics,Southern Medical University,Guangzhou 510515,China)

机构地区：[1]广东医科大学,广东湛江524000 [2]惠州市第一人民医院神经内科,广东惠州516003 [3]南方医科大学遗传学教研室,广东广州510515

出　　处：《中山大学学报（医学版）》2019年第1期83-89,共7页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：广东省自然科学基金(2015A030313834)

摘　　要：【目的】对一个早发性家族性阿尔茨海默病家系(EOFAD)进行全外显子组测序,寻找可能引起致病的突变位点,为遗传咨询和产前诊断提供参考。【方法】对该家系成员进行全外显子基因检测,随后运用Poly?Phen-2和SIFT等生物信息学软件进行突变基因有害性预测。【结果】测序结果显示家系中患者在TTC3基因的第9个外显子发生c.758A>G突变,导致所编码的TTC3蛋白的第253位氨基酸由原来的酪氨酸变为半胱氨酸(p.Tyr253Cys)。根据家系共分离及相关生物信息学分析得出该突变基因为可能致病的变异。【结论】TTC3基因第9个外显子c.758A>G突变为该EOFAD家系可能致病的原因,该突变为首次发现报道。本结果扩展了TTC3基因突变谱,为家系遗传咨询提供了依据。【Objective】A full exome sequencing of an early-onset family Alzheimer′s disease(EOFAD)was conduct.ed to identify the mutational sites which may cause diseases.The result of the current study may provide suggestion to ge.netic counseling and prenatal diagnosis.【Methods】Whole exome sequencing was performed on the family members and software PolyPhen-2 as well as SIFT was employed for hazard prediction(Prediction on functional effects of the missense mutation).【Results】The heterozygous mutation c.758A >G(p.Tyr253Cys)in exon 9 of TTC3 gene had been identified in proband whose mother had been proved with heterozygous mutation c.758A >G.According to the family separation and re.lated bioinformatics analysis,the mutant gene was a possible pathogenic mutation.【Conclusion】A new mutation was found of c.758A >G in TTC3 gene within a Chinese EOFAD family and a new mutation to the spectrum of genetic mutation in EOFAD was expanded.The finding provides a significant groundwork for future exploration on the mechanisms underly.ing EOFAD.

关 键 词：家族性阿尔茨海默病 TTC3基因 突变分析 

分 类 号：R74[医药卫生—神经病学与精神病学]