Clinical features of frontotemporal dementia due to the intronic tau 10+16 mutation
Clinical features of frontotemporal dementia due to the intronic tau 10+16 mutation
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DOI：
10.1212/wnl.58.8.1161
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发表时间：
2002-04-23
期刊：
影响因子：
9.9
通讯作者：
Rossor, MN
中科院分区：
文献类型：
--
作者：
Janssen, JC;Warrington, EK;Rossor, MN
目的：描述9个英国家庭的临床特征，这些家庭患有经神经病理学证实的因内含子tau外显子10（+16）突变而导致的额颞叶痴呆（FTD）。研究方法：对属于9个tau 10（+16）突变谱系的FTD家庭成员进行了回顾性图表审查，并对其进行了神经病理学检查。对于那些有DNA的患者，确定APOE基因型。结果：发病时的中位年龄为50岁（范围37 - 59岁; n = 30）。死亡时的中位年龄为61岁（范围42 - 72岁; n = 33）。死亡患者的中位病程为11年（范围3至22年; n = 25），存活患者的中位病程为17年（范围15至23年; n = 3）。最常见的症状是抑制解除（n = 23）。少数人表现出额叶执行障碍症状、冷漠、情景记忆受损或抑郁。所有这些患者随后都出现了性格和行为变化。记忆障碍、语言缺陷、仪式行为、食欲过盛和食欲亢进是常见症状。帕金森综合征，抗精神病药敏感性，或原始反射，在一半的患者，这些数据是可用的。ALS的临床特征不存在。12名患者的神经病理学检查显示出标志性的tau阳性神经元和神经胶质内含物。APOE基因型不能解释发病年龄、死亡年龄、病程或估计的脑萎缩严重程度的显著差异。结论：所有病例均符合FTD诊断的临床标准。尽管有相似的临床表型，有相当大的变化，在发病年龄和疾病的持续时间之间和家庭内，这表明存在的影响，由于其他遗传或环境因素。
Objective: To describe the clinical features of nine British families with neuropathologically verified frontotemporal dementia (FTD) due to the intronic tau exon 10(+16) mutation. Methods: Retrospective chart reviews of family members with FTD belonging to nine tau 10(+16) mutation pedigrees in whom neuropathologic examination had been carried out. APOE genotype was determined for those patients for whom DNA was available. Results: The median age at onset was 50 years (range 37 to 59 years; n = 30). The median age at death was 61 years (range 42 to 72 years; n = 33). The median duration of the disease was 11 years (range 3 to 22 years; n = 25) for those who have died and is 17 years (range 15 to 23 years; n = 3) for those living. The most common presenting symptom was disinhibition (n = 23). A minority presented with frontal dysexecutive symptoms, apathy, impairment of episodic memory, or depression. All of these patients subsequently developed personality and behavioral change. Memory impairment, language deficits, ritualistic behavior, hyperphagia, and hyperorality were frequent symptoms. Parkinsonism, neuroleptic sensitivity, or primitive reflexes were present in half of the patients, where these data were available. The clinical features of ALS were absent. Neuropathologic examination of 12 patients demonstrated the hallmark tau-positive neuronal and glial inclusions. APOE genotype did not account for the considerable variation in age at onset, age at death, duration of disease, or severity of estimated brain atrophy. Conclusions: All cases fulfilled the clinical criteria for a diagnosis of FTD. Despite similar clinical phenotypes, there was considerable variation in age at onset and duration of disease both between and within families, suggesting the presence of an effect due to other genetic or environmental factors.