The genetics of primary progressive aphasia
The genetics of primary progressive aphasia
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原发性进行性失语症的遗传学
DOI：
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发表时间：
2014
期刊：
影响因子：
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通讯作者：
J. Rohrer
中科院分区：
文献类型：
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作者：
J. Rohrer
背景：原发性进行性失语症（PPA）是一种以语言障碍为首发症状和主要症状的疾病。描述了三种主要表型，非流利变体（nfvPPA）、语义变体（svPPA）和语词减少变体（lvPPA）。尽管 PPA 最常见的是一种散发性疾病，但最近的研究表明 PPA 与许多基因突变有关。目的：了解 PPA 的遗传程度、哪些基因突变可能导致 PPA，以及遗传性 PPA 的表型是否与散发性 PPA 不同。主要贡献：尽管nfvPPA比svPPA和lvPPA（通常都是散发性疾病）更具遗传性，但大约20-30%的PPA患者存在家族史。颗粒体蛋白前体 (GRN) 和 9 号染色体开放阅读框 72 (C9orf72) 基因的突变是遗传性 PPA 的主要原因。结论：可能建议检测 PPA 中 GRN 突变的关键指标是额颞叶痴呆谱系中的一种疾病（nfvPPA 表型）的家族史，特别是在出现明显的贫血和不对称额颞顶叶萎缩的情况下。对于患有 nfvPPA 且有家族史的人，应首先测试 GRN，但如果呈阴性，则应搜索 C9orf72 基因中的六核苷酸重复扩展，特别是如果存在运动神经元疾病的特征或有运动神经元疾病的家族史。其他基因突变只是 PPA 的非常罕见的原因，但如果 GRN 和 C9orf72 均为阴性，则应考虑检测微管相关蛋白 tau (MAPT)、含缬洛辛蛋白 (VCP) 和早老素 1 (PSEN1) 的突变。
Background: Primary progressive aphasia (PPA) is a disorder in which language impairment is the initial and predominant symptom. Three main phenotypes are described, the nonfluent variant (nfvPPA), the semantic variant (svPPA) and the logopenic variant (lvPPA). Although PPA is most commonly a sporadic disorder, recent studies have shown an association of PPA with mutations in a number of genes. Aims: To understand the extent to which PPA may be inherited, which genetic mutations may cause it, and whether the phenotypes of genetic PPA differ from sporadic PPA. Main Contribution: In around 20–30% of patients with PPA, a family history is present although nfvPPA is more heritable than svPPA and lvPPA which are both usually sporadic disorders. Mutations in the progranulin (GRN) and chromosome 9 open reading frame 72 (C9orf72), genes are the major causes of genetic PPA. Conclusions: Key pointers that may suggest testing for a GRN mutation in PPA are a family history of one of the disorders within the frontotemporal dementia spectrum, a nfvPPA phenotype, particularly if presenting with a prominent anomia and asymmetrical fronto-temporo-parietal atrophy. In someone with nfvPPA and a family history, GRN should be tested initially but a search for hexanucleotide repeat expansions in the C9orf72 gene should be performed if negative, particularly if there are features of motor neurone disease, or a family history of someone with motor neurone disease. Mutations in other genes are only very rare causes of PPA but if GRN and C9orf72 are both negative, testing for mutations in the microtubule-associated protein tau (MAPT), valosin-containing protein (VCP) and presenilin 1 (PSEN1) should be considered.
影响因子：
14.5
作者：
Josephs, Keith A.;Duffy, Joseph R.;Petersen, Ronald C.
通讯作者：
Petersen, Ronald C.