漸凍人癥的學(xué)名為肌萎縮性脊髓側(cè)索硬化癥（英文縮寫：ALS）,，其癥狀表現(xiàn)為由于上、下運(yùn)動(dòng)神經(jīng)元退化和死亡并停止傳送訊息到肌肉,，肌肉逐漸衰弱,、萎縮，以致最后大腦完全喪失控制肌肉的能力,。著名英國(guó)物理學(xué)家史提芬.霍金患的即是此癥,。癡呆癥又名額顳葉癡呆癥（英文縮寫：FTD），美國(guó)前總統(tǒng)里根,、拳王阿里等皆患此癥,。ALS和FTD的臨床癥狀很不相同，但在某些人身上又有一些相似的地方,。2006年,，研究人員確認(rèn)此兩種病癥源于9號(hào)染色體中的某個(gè)變異基因，但沒能確定具體是哪個(gè)基因的突變導(dǎo)致這些疾病,，于是展開了一場(chǎng)尋找特定基因的賽跑,。
近日，美國(guó)梅奧醫(yī)院（Mayo Clinic）的Rosa Rademakers醫(yī)生領(lǐng)導(dǎo)的小組和國(guó)家老年病研究所（National Institute on Aging）的Bryan Traynor領(lǐng)導(dǎo)的小組分別獨(dú)立地發(fā)現(xiàn)以上兩種病癥源于同一個(gè)基因的突變,，該基因就是C9ORF72,。Rademakers說，這個(gè)基因很不起眼,，醫(yī)生們過去對(duì)它的功能一無所知,，但它現(xiàn)在是圈內(nèi)每個(gè)人都等待已久的謎底。
上述發(fā)現(xiàn)發(fā)表在9月21日的《神經(jīng)元》（Neuron）雜志網(wǎng)絡(luò)版上,。有專家評(píng)論說,，這是領(lǐng)域內(nèi)的一大進(jìn)步，醫(yī)生們終于找到了罪魁禍?zhǔn)?；下一步他們將著手解答何種突變導(dǎo)致ALS何種突變導(dǎo)致FTD,，以及這兩種疾病的致病機(jī)理方面的問題。（生物谷 Bioon.com）
doi:0.1016/j.neuron.2011.09.010
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PMID:
A Hexanucleotide Repeat Expansion in C9ORF72 Is the Cause of Chromosome 9p21-Linked ALS-FTD
Alan E. Renton, Elisa Majounie, Adrian Waite, Javier Simón-Sánchez, Sara Rollinson, J. Raphael Gibbs, Jennifer C. Schymick, Hannu Laaksovirta, John C. van Swieten, Liisa Myllykangas, Hannu Kalimo, Anders Paetau, Yevgeniya Abramzon, Anne M. Remes, Alice Kaganovich, Sonja W. Scholz, Jamie Duckworth, Jinhui Ding, Daniel W. Harmer, Dena G. Hernandez, Janel O. Johnson, Kin Mok, Mina Ryten, Danyah Trabzuni, Rita J. Guerreiro, Richard W. Orrell, James Neal, Alex Murray, Justin Pearson, Iris E. Jansen,
The chromosome 9p21 amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD) locus contains one of the last major unidentified autosomal-dominant genes underlying these common neurodegenerative diseases. We have previously shown that a founder haplotype, covering the MOBKL2b, IFNK, and C9ORF72 genes, is present in the majority of cases linked to this region. Here we show that there is a large hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72 on the affected haplotype. This repeat expansion segregates perfectly with disease in the Finnish population, underlying 46.0% of familial ALS and 21.1% of sporadic ALS in that population. Taken together with the D90A SOD1 mutation, 87% of familial ALS in Finland is now explained by a simple monogenic cause. The repeat expansion is also present in one-third of familial ALS cases of outbred European descent, making it the most common genetic cause of these fatal neurodegenerative diseases identified to date.
doi:0.1016/j.neuron.2011.09.011
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Expanded GGGGCC Hexanucleotide Repeat in Noncoding Region of C9ORF72 Causes Chromosome 9p-Linked FTD and ALS
Mariely DeJesus-Hernandez, Ian R. Mackenzie, Bradley F. Boeve, Adam L. Boxer, Matt Baker, Nicola J. Rutherford, Alexandra M. Nicholson, NiCole A. Finch, Heather Flynn, Jennifer Adamson, Naomi Kouri, Aleksandra Wojtas, Pheth Sengdy, Ging-Yuek R. Hsiung, Anna Karydas, William W. Seeley, Keith A. Josephs, Giovanni Coppola, Daniel H. Geschwind, Zbigniew K. Wszolek, Howard Feldman, David S. Knopman, Ronald C. Petersen, Bruce L. Miller, Dennis W. Dickson, Kevin B. Boylan, Neill R. Graff-Radford, Rosa
everal families have been reported with autosomal-dominant frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), genetically linked to chromosome 9p21. Here, we report an expansion of a noncoding GGGGCC hexanucleotide repeat in the gene C9ORF72 that is strongly associated with disease in a large FTD/ALS kindred, previously reported to be conclusively linked to chromosome 9p. This same repeat expansion was identified in the majority of our families with a combined FTD/ALS phenotype and TDP-43-based pathology. Analysis of extended clinical series found the C9ORF72 repeat expansion to be the most common genetic abnormality in both familial FTD (11.7%) and familial ALS (23.5%). The repeat expansion leads to the loss of one alternatively spliced C9ORF72 transcript and to formation of nuclear RNA foci, suggesting multiple disease mechanisms. Our findings indicate that repeat expansion in C9ORF72 is a major cause of both FTD and ALS.
