?科學(xué)家最近發(fā)現(xiàn)一種新的基因可能與罕見的神經(jīng)系統(tǒng)疾病--遺傳性痙攣性截癱有關(guān),，該疾病目前尚無(wú)有效的治療方法,。
??杜克大學(xué)醫(yī)學(xué)中心的研究人員聲稱，這項(xiàng)發(fā)現(xiàn)將帶來(lái)藥物的變革以針對(duì)該致病基因,。
??6-7%的遺傳性痙攣性截癱患者存在該基因缺陷,。杜克研究中心人類基因?qū)W和精神病學(xué)助理教授Stephan Züchner博士說(shuō)，這項(xiàng)發(fā)現(xiàn)將為其他神經(jīng)變性疾病提供一些重大的思考,，如肌萎縮性脊髓側(cè)索硬化癥或俗稱葛雷克氏癥(Lou Gehrig氏癥),。
??“這些基因缺陷導(dǎo)致的疾病目前還沒(méi)有真正有效的治療措施，”該研究小組的負(fù)責(zé)人Züchner說(shuō),，“我們的發(fā)現(xiàn)會(huì)從嶄新的角度帶來(lái)新的研究方法,，因此我們將能更好的理解其發(fā)病原因，以及該針對(duì)哪些基因來(lái)設(shè)計(jì)治療方法,。”
??遺傳性痙攣性截癱是一種遺傳性疾病,，患者癥狀是下肢進(jìn)行性萎縮和僵直，其中大多最終將癱瘓,。和許多神經(jīng)變性疾病一樣,，典型的病人從20歲到50歲之間開始出現(xiàn)病癥，而隨著時(shí)間推移癥狀進(jìn)行性加重,。由于沒(méi)有徹底有效的治療措施,，醫(yī)生只能采取一些物理療法來(lái)改善肌肉力量和保持運(yùn)動(dòng)能力。
??杜克的研究人員發(fā)現(xiàn)其中一種遺傳性痙攣性截癱與REEP1基因有關(guān),。該基因通常編碼支持細(xì)胞能量源泉—線粒體的蛋白質(zhì),。但缺陷基因卻不同產(chǎn)生蛋白質(zhì)以維持線粒體的正常功能—尤其是神經(jīng)系統(tǒng)細(xì)胞通路的線粒體。杜克人類基因?qū)W研究中心主任及該研究的負(fù)責(zé)人Margaret Pericak-Vance博士說(shuō)，目前尚不清楚這類蛋白質(zhì)究竟如何發(fā)生故障,。
??杜克研究中心的科學(xué)家們研究了兩個(gè)存在遺傳性痙攣性截癱患者的家庭,。
??研究人員運(yùn)用基因制圖技術(shù)鑒定了2號(hào)染色體上的一小段DNA，而通常認(rèn)為致病基因就存在于該染色體,。研究人員還檢測(cè)了9名志愿者的基因,，這些基因在控制神經(jīng)變性疾病的細(xì)胞通路上發(fā)揮著潛在的作用。研究人員仔細(xì)檢查了這些基因的DNA順序,，并定位了遺傳性痙攣性截癱患者的REEP1基因突變,。
??Pericak-Vance及同事 Allison Ashley-Koch博士說(shuō)，遺傳性痙攣性截癱患者REEP1基因作用的發(fā)現(xiàn)更進(jìn)一步證明了,，線粒體功能的缺陷是許多神經(jīng)變性疾病的原因,。例如，科學(xué)家已經(jīng)發(fā)現(xiàn)葛雷克氏癥是由于SOD1基因突變,，而該基因編碼的蛋白質(zhì)也在線粒體里表達(dá)。
??鑒于REEP1作用的發(fā)現(xiàn),，科學(xué)家們正設(shè)計(jì)一種基因檢查來(lái)診斷存在該基因缺陷的病人,，Züchner說(shuō)道。杜克大學(xué)研究小組已經(jīng)將其成果轉(zhuǎn)讓Athena 技術(shù)公司以開發(fā)相關(guān)基因檢查,。
英文原文：
Duke Researchers Link Newly Discovered Gene to Hereditary Neurological Disease
July 13, 2006
DURHAM, N.C. -- Scientists have linked a recently discovered gene to a rare nervous system disease called hereditary spastic paraplegia, for which there is no cure.
The discovery could lead to development of drugs that target the defective gene, said the researchers at Duke University Medical Center who discovered the mutation.
The gene defect accounts for 6 percent to 7 percent of all cases of hereditary spastic paraplegia, they said. The discovery of the gene defect will provide important insights into the causes of other major neurodegenerative diseases, including amyotrophic lateral sclerosis or Lou Gehrig's disease, said Stephan Züchner, M.D., assistant professor at the Duke Center for Human Genetics and the Department of Psychiatry.
"Patients with these genetic diseases now have no real treatment options," said Züchner, co-leader of the study team. "Our discovery will open up a new opportunity to study these diseases from a different angle so we can better understand what is causing them and which genes to target in developing treatments to manage them."
The researchers report their findings in the August 2006 issue of the American Journal of Human Genetics, which is now available online. The research was funded by the National Institutes of Health and by donations to the Duke Center for Human Genetics from individuals and families affected by hereditary spastic paraplegia.
Hereditary spastic paraplegia, one of a number of related inherited disorders, causes progressive limb weakness and stiffness, often resulting in paralysis. As with many neurodegenerative diseases, patients typically begin to show symptoms during their mid-20s to mid-50s, and the symptoms grow progressively more debilitating with time. With no cure available, physicians can only treat symptoms with physical therapy to improve muscle strength and preserve range of motion.
In their study, the Duke researchers found that one form of hereditary spastic paraplegia is linked to a gene called REEP1. The gene normally produces proteins that support the cell's energy source, the mitochondria. But a defect in the gene may disable its proteins from performing their normal functions in mitochondria – most notably the mitochondria within the nervous system's cellular pathways. Precisely how this protein malfunction occurs is still unknown, said Margaret Pericak-Vance, Ph.D., director of Duke's Center for Human Genetics and co-leader of the study.
The Duke scientists began their search for genes associated with the disease by studying two families whose members had hereditary spastic paraplegia.
Using gene-mapping techniques, the researchers identified a small stretch of DNA on chromosome 2, where the disease-causing gene was thought to reside. The researchers screened nine candidate genes that play a potential role in governing the cellular pathways of neurodegenerative disease. By meticulously examining the DNA sequence of those genes, the researchers located mutations -- changes in the DNA sequence -- in the REEP1 gene among people who have hereditary spastic paraplegia but not in their unaffected relatives.
Pericak-Vance and team member Allison Ashley-Koch, Ph.D., said that the discovery of REEP1's role in hereditary spastic paraplegia strengthens the evidence that defects in mitochondria are responsible for many types of neurodegenerative diseases. For example, scientists have discovered that Lou Gehrig's disease is caused by mutations in SOD1, a gene whose protein is also expressed in mitochondria.
With REEP1's role now identified, scientists are developing a genetic test to identify patients who have the defect, Züchner said. The Duke team has licensed its gene discovery to Athena Diagnostics Inc. to develop a genetic test for patients at risk for the disease.
Other members of the research team were Gaofeng Wang, Khan Nhat Trans Viet, Martha Nance, Perry Gaskell and Jeffrey Vance.
