Clinical and pathological features of amyotrophic lateral sclerosis caused by mutation in the C9ORF72 gene on chromosome 9p.
Clinical and pathological features of amyotrophic lateral sclerosis caused by mutation in the C9ORF72 gene on chromosome 9p.
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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。
DOI：
10.1007/s00401-011-0937-5
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发表时间：
2012-03
影响因子：
12.7
通讯作者：
Mackenzie IR
中科院分区：
文献类型：
--
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
最近有两项研究发现，染色体9p连锁的肌萎缩侧索硬化症(ALS)和额颞性痴呆(FTD)的病因是9号染色体开放阅读框72基因(C9ORF72)非编码区的GGGGCC六核苷酸重复序列扩张。在231例ALS先证者的队列中，我们发现17例家族性(27.4%)和6例散发(3.6%)的C9ORF72突变。带有C9ORF72突变的患者表现出典型的ALS运动特征，尽管与没有该突变的患者相比，C9ORF72突变的患者有更频繁的延髓发作。痴呆在ALS患者和具有C9ORF72突变的家庭中明显更常见，通常是早发性FTD。携带该突变的个体家系成员之间存在显著的临床异质性。相关的神经病理是ALS合并TDP-ir包涵体和FTLD-TDP。除了TDP-43免疫反应阳性的病理，C9ORF72突变病例的一个一致和特殊的特征是在各种神经解剖区域存在泛素阳性而TDP-43阴性的包涵体，如小脑皮质。这些发现支持C9ORF72突变是ALS的一个新的重要原因，提供了与ALS相关的临床和病理特征的更详细的特征，并进一步证明了ALS和FTD之间的临床和分子重叠。
Two studies recently identified a GGGGCC hexanucleotide repeat expansion in a non-coding region of the chromosome 9 open reading frame 72 gene (C9ORF72) as the cause of chromosome 9p-linked amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In a cohort of 231 probands with ALS, we identified the C9ORF72 mutation in 17 familial (27.4 %) and six sporadic (3.6%) cases. Patients with the mutation presented with typical motor features of ALS, although subjects with the C9ORF72 mutation had more frequent bulbar onset, compared to those without this mutation. Dementia was significantly more common in ALS patients and families with the C9ORF72 mutation and was usually early-onset FTD. There was striking clinical heterogeneity among the members of individual families with the mutation. The associated neuropathology was a combination of ALS with TDP-ir inclusions and FTLD-TDP. In addition to TDP-43-immunoreactive pathology, a consistent and specific feature of cases with the C9ORF72 mutation was the presence of ubiquitin-positive, TDP-43-negative inclusions in a variety of neuroanatomical regions, such as the cerebellar cortex. These findings support the C9ORF72 mutation as an important newly-recognized cause of ALS, provide a more detailed characterization of the associated clinical and pathological features and further demonstrate the clinical and molecular overlap between ALS and FTD.
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影响因子：
48
作者：
Laaksovirta, Hannu;Peuralinna, Terhi;Schymick, Jennifer C.;Scholz, Sonja W.;Lai, Shaoi-Lin;Myllykangas, Liisa;Sulkava, Raimo;Jansson, Lilja;Hernandez, Dena G.;Gibbs, J. Raphael;Nalls, Michael A.;Heckerman, David;Tienari, Pentti J.;Traynor, Bryan J.
通讯作者：
Traynor, Bryan J.
影响因子：
6
作者：
Pearson, Justin P.;Williams, Nigel M.;Morris, Huw R.
通讯作者：
Morris, Huw R.
影响因子：
6
作者：
Cairns, Nigel J.;Neumann, Manuela;Mackenzie, Ian R. A.
通讯作者：
Mackenzie, Ian R. A.
影响因子：
12.7
作者：
Al-Sarraj, Safa;King, Andrew;Shaw, Christopher E.
通讯作者：
Shaw, Christopher E.
具有额颞叶变性的谱系 - 运动神经元疾病和焦油DNA结合蛋白-43阳性神经病理学：与9号染色体的遗传联系。
影响因子：
2.6
作者：
Luty, Agnes A.;Kwok, John B. J.;Thompson, Elizabeth M.;Blumbergs, Peter;Brooks, William S.;Loy, Clement T.;Dobson-Stone, Carol;Panegyres, Peter K.;Hecker, Jane;Nicholson, Garth A.;Halliday, Glenda M.;Schofield, Peter R.
通讯作者：
Schofield, Peter R.