MAPT基因突变所致额颞叶痴呆家系临床及影像学特征分析
贺爽;陈帅;夏明荣;任治侠;孙治坤;张杰文;
摘要(Abstract)：
目的报道1例行为变异型额颞叶痴呆(bv-FTD)家系,分析该家系的临床和影像学特征,并行基因诊断。方法对该家系进行调查、详细的病史询问、体格检查,行神经影像学检查(头颅磁共振成像、18F-氟脱氧葡萄糖(FDG)正电子发射断层扫描(PET-CT)和动脉自旋标记核磁灌注成像(ASL-MRI)。对相关致病基因(MAPT、PSEN1、PSEN2、APP)进行直接测序筛查突变。结果先证者基因检测发现MAPT基因P301L位点致病突变。该先证者及家系其他患者均表现为以行为变异型FTD(bvFTD),无帕金森病样表现。结构影像学检查见双侧额颞叶不对称萎缩,功能影像见额颞叶低代谢和低灌注。临床特征和影像学结果支持bv-FTD诊断。家系内患者临床表型高度一致。结论我们报道1例MAPT P301L突变家系,神经影像和基因检测有助于家族史阳性痴呆患者的诊断。
关键词(KeyWords)： 额颞叶痴呆;基因检测;神经影像;基因突变;遗传学特征
基金项目(Foundation): 国家自然科学基金面上项目,编号:81671068
作者(Authors): 贺爽;陈帅;夏明荣;任治侠;孙治坤;张杰文;
参考文献(References)：
- [1]OLSZEWSKA D A,LONERGAN R,FALLON E M,et al.Genetics of Frontotemporal Dementia[J].Curr Neurol Neurosci Rep,2016,16(12):107.
- [2]KASUGA K,KIKUCHI M,TOKUTAKE T,et al.Systematic review and meta-analysis of Japanese familial Alzheimer’s disease and FTDP-17[J].Journal of human genetics,2015,60(5):281-283.
- [3]OGAKI K,LI Y,TAKANASHI M,et al.Analyses of the MAPT,PGRN,and C9orf72 mutations in Japanese patients with FTLD,PSP,and CBS[J].Parkinsonism Relat Disord,2013,19(1):15-20.
- [4]KIM E J,KWON J C,PARK K H,et al.Clinical and genetic analysis of MAPT,GRN,and C9orf72 genes in Korean patients with frontotemporal dementia[J].Neurobiol Aging,2014,35(5):1 213.e13-17.
- [5]TANG M,GU X,WEI J,et al.Analyses MAPT,GRN,and C9orf72 mutations in Chinese patients with frontotemporal dementia[J].Neurobiol Aging,2016,46:235.e11-15.
- [6]SHI Z,LIU S,XIANG L,et al.Frontotemporal dementiarelated gene mutations in clinical dementia patients from a Chinese population[J].J Hum Genet,2016,61(12):1003-1 008.
- [7]YANG Y,TANG B S,WENG L Y,et al.Genetic Identification Is Critical for the Diagnosis of Parkinsonism:A Chinese Pedigree with Early Onset of Parkinsonism[J].PLo S One,2015,10(8):e0136245.
- [8]武力勇,冯雪岩,历含之,等.家族性额颞叶痴呆合并帕金森综合征临床和影像学特征分析[J].中华神经科杂志,2017,50(1):11-16.
- [9]李明月.额颞叶痴呆一家系研究及额颞叶痴呆临床特征回顾性分析[D].南方医科大学,2015.DOI:10.7666/d.Y2911368.
- [10]SUN L,CHEN K,LI X,XIAO S.Rapidly Progressive Frontotemporal Dementia Associated with MAPT Mutation G389R[J].J Alzheimers Dis,2017,55(2):777-785.
- [11]SIUDA J,FUJIOKA S,WSZOLEK Z K.Parkinsonian syndrome in familial frontotemporal dementia[J].Parkinsonism Relat Disord,2014,20(9):957-964.
- [12]BORREGO-CIJA S,MORGADO J,PALENCIAMADRID L,et al.Frontotemporal Dementia Caused by the P301L Mutation in the MAPT Gene:Clinicopathological Features of 13 Cases from the Same Geographical Origin in Barcelona,Spain[J].Dement Geriatr Cogn Disord,2017,44(3-4):213-221.
- [13]GATTO E M,ALLEGRI R F,Da PRAT G,et al.Intrafamilial variable phenotype including corticobasal syndrome in a family with p.P301L mutation in the MAPT gene:first report in South America[J].Neurobiol Aging,2017,53:e11-17.
- [14]SITEK E J,NAROZANSKA E,BARCZAK A,et al.Agraphia in patients with frontotemporal dementia and parkinsonism linked to chromosome 17 with P301L MAPT mutation:dysexecutive,aphasic,apraxic or spatial phenomenon?[J].Neurocase,2014,20(1):69-86.
- [15]KODAMA K,OKADA S,ISEKI E.Familial frontotemporal dementia with a P301L tau mutation in Japan[J].Journal of the Neurological Sciences,2000,176:57-64.
- [16]ISHIZUKA T,NAKAMURA M,ICHIBA M,et al.Familial semantic dementia with P301L mutation in the Tau gene[J].Dement Geriatr Cogn Disord,2011,31(5):334-340.
- [17]TSUBOI Y,BAKER M,HUTTON M L,et al.Clinical and genetic studies of families with the tau N279K mutation(FTDP-17)[J].Neurology,2002,59(11):1 791-1 793.
- [18]TOSUN D,SCHUFF N,RABINOVICI G D,et al.Diagnostic utility of ASL-MRI and FDG-PET in the behavioral variant of FTD and AD[J].Ann Clin Transl Neurol,2016,3(10):740-751.
- [19]VERFAILLIE S C,ADRIAANSE S M,BINNEWIJZEND M A,et al.Cerebral perfusion and glucose metabolism in Alzheimer’s disease and frontotemporal dementia:two sides of the same coin?[J].Eur Radiol,2015,25(10):3050-3 059.
- [20]DU A T,JAHNG G H,HAYASAKA S,et al.Hypoperfusion in frontotemporal dementia and Alzheimer disease by arterial spin labeling MRI[J].Neurology,2006,67(7):1 215-1 220.