A pathogenic progranulin mutation and C9orf72 repeat expansion in a family with frontotemporal dementia.
A pathogenic progranulin mutation and C9orf72 repeat expansion in a family with frontotemporal dementia.
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DOI：
10.1111/nan.12100
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发表时间：
2014-06
影响因子：
5
通讯作者：
Revesz T
中科院分区：
文献类型：
--
作者：
Lashley T;Rohrer JD;Mahoney C;Gordon E;Beck J;Mead S;Warren J;Rossor M;Revesz T
额颞叶变性（FTLD）是一种进行性神经退行性疾病，是仅次于阿尔茨海默病（AD）的第二种最常见的年轻痴呆形式。常染色体显性遗传模式存在于约25-50%的FTLD病例中，表明具有很强的遗传成分。FTLD的主要致病突变已被证明独立于颗粒蛋白前体（GRN）基因和C9 orf 72六核苷酸扩增重复序列。在这项研究中，我们提出了一个家庭，已被确定为携带GRN Cys 31 fs突变和C9 orf 72六核苷酸扩增重复。在本研究中，我们描述了临床和遗传的家庭成员的细节和病理特征的两个家庭成员，已经来到验尸。发病时的平均年龄为57岁（48-61岁），平均病程为4年（2-7年）。最常见的症状是行为变异性额颞叶痴呆。现有病例的脑成像显示对称性萎缩，特别是影响额叶和颞叶。病理学上2例被归类为FTLD-TDP A型，TDP-43阳性包涵体，在海马结构和小脑中发现额外的p62阳性“星形”包涵体。这两例患者的病理类型和分布与仅携带C9 orf 72六核苷酸重复序列的FTLD患者一致。然而，病理过程的驱动力可能是致病突变或两者的组合，集中在一个单一的机制。
Frontotemporal lobar degeneration (FTLD) is a progressive neurodegenerative disease and is the second most common form of young onset dementia after Alzheimer's disease (AD). An autosomal dominant pattern of inheritance is present in around 25–50% of FTLD cases indicating a strong genetic component. Major pathogenic mutations of FTLD have been demonstrated independently in the progranulin (GRN) gene and the C9orf72 hexanucleotide expansion repeat. In this study we present a family that have been identified as carrying both a GRN Cys31fs mutation and the C9orf72 hexanucleotide expansion repeat. In the present study we describe the clinical and genetic details of family members and pathological features of two family members that have come to post-mortem. The mean age at disease onset was 57 years (48–61 years) and mean duration 4 years (2–7 years). The most common presenting syndrome was behavioural variant frontotemporal dementia. Brain imaging from available cases showed a symmetrical pattern of atrophy particularly affecting the frontal and temporal lobes. Pathologically two cases were classified as FTLD-TDP type A with TDP-43 positive inclusions, with additional p62-positive ‘star-like’ inclusions found in the hippocampal formation and cerebellum. The type and distribution of the pathological lesions in these two cases were in keeping with FTLD cases carrying only the C9orf72 hexanucleotide repeat. However the driving force of the pathological process may be either pathogenic mutation or a combination of both converging on a singular mechanism.
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由C9orf72基因在9p染色体上突变引起的肌萎缩性侧索硬化症的临床和病理特征。
影响因子：
12.7
作者：
Stewart H;Rutherford NJ;Briemberg H;Krieger C;Cashman N;Fabros M;Baker M;Fok A;DeJesus-Hernandez M;Eisen A;Rademakers R;Mackenzie IR
通讯作者：
Mackenzie IR
DOI：
10.1093/brain/aws001
发表时间：
2012-03
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Whitwell JL;Weigand SD;Boeve BF;Senjem ML;Gunter JL;DeJesus-Hernandez M;Rutherford NJ;Baker M;Knopman DS;Wszolek ZK;Parisi JE;Dickson DW;Petersen RC;Rademakers R;Jack CR Jr;Josephs KA
通讯作者：
Josephs KA
影响因子：
9.9
作者：
Rohrer, J. D.;Guerreiro, R.;Rossor, M. N.
通讯作者：
Rossor, M. N.
影响因子：
12.7
作者：
Al-Sarraj, Safa;King, Andrew;Shaw, Christopher E.
通讯作者：
Shaw, Christopher E.
影响因子：
14.5
作者：
Lashley, Tammaryn;Rohrer, Jonathan D.;Revesz, Tamas
通讯作者：
Revesz, Tamas