Phenotypic Heterogeneity of Monogenic Frontotemporal Dementia.
Phenotypic Heterogeneity of Monogenic Frontotemporal Dementia.
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DOI：
10.3389/fnagi.2015.00171
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发表时间：
2015
影响因子：
4.8
通讯作者：
Borroni B
中科院分区：
文献类型：
--
作者：
Benussi A;Padovani A;Borroni B
额颞叶痴呆(FTD)是一种遗传和病理上的异质性疾病，其特征是个性改变、语言障碍以及与额叶和颞叶退变相关的执行功能缺陷。根据临床症状的不同，定义了不同的表型，即FTD的行为变异型、原发进行性失语的失语型变异型和PPA的语义变异型。一些患者有相关的运动障碍，如进行性核上性瘫痪和皮质-基底综合征中的帕金森综合症，或运动神经元病(FTD-MND)。40%的FTD患者有痴呆家族史，约10%的患者有明显的常染色体显性遗传。遗传学研究已经确定了几个与单基因FTD相关的基因：微管相关蛋白tau、原颗粒蛋白、TAR DNA结合蛋白43、含有Valosin的蛋白、在肉瘤中融合的带电多囊体蛋白2B，以及在9号染色体开放阅读框架72的内含子1中的六核苷酸重复扩增。患者经常表现出广泛的表型变异，即使在携带相同疾病突变的同一家族的不同成员之间也是如此。本研究的目的是回顾和评估现有的文献资料，以突出单基因额颞叶变性的临床、生物学和神经影像特征的最新进展，并试图确定这种疾病的极端表型异质性背后的不同机制。
Frontotemporal dementia (FTD) is a genetically and pathologically heterogeneous disorder characterized by personality changes, language impairment, and deficits of executive functions associated with frontal and temporal lobe degeneration. Different phenotypes have been defined on the basis of presenting clinical symptoms, i.e., the behavioral variant of FTD, the agrammatic variant of primary progressive aphasia, and the semantic variant of PPA. Some patients have an associated movement disorder, either parkinsonism, as in progressive supranuclear palsy and corticobasal syndrome, or motor neuron disease (FTD–MND). A family history of dementia is found in 40% of cases of FTD and about 10% have a clear autosomal-dominant inheritance. Genetic studies have identified several genes associated with monogenic FTD: microtubule-associated protein tau, progranulin, TAR DNA-binding protein 43, valosin-containing protein, charged multivesicular body protein 2B, fused in sarcoma, and the hexanucleotide repeat expansion in intron 1 of the chromosome 9 open reading frame 72. Patients often present with an extensive phenotypic variability, even among different members of the same kindred carrying an identical disease mutation. The objective of the present work is to review and evaluate available literature data in order to highlight recent advances in clinical, biological, and neuroimaging features of monogenic frontotemporal lobar degeneration and try to identify different mechanisms underlying the extreme phenotypic heterogeneity that characterizes this disease.