?科学家最近发现一种新的基因可能与罕见的神经系统疾病--遗传性痉挛性截瘫有关，该疾病目前尚无有效的治疗方法。
??杜克大学医学中心的研究人员声称，这项发现将带来药物的变革以针对该致病基因。
??6-7%的遗传性痉挛性截瘫患者存在该基因缺陷。杜克研究中心人类基因学和精神病学助理教授Stephan Züchner博士说，这项发现将为其他神经变性疾病提供一些重大的思考，如肌萎缩性脊髓侧索硬化症或俗称葛雷克氏症(Lou Gehrig氏症)。
??“这些基因缺陷导致的疾病目前还没有真正有效的治疗措施，”该研究小组的负责人Züchner说，“我们的发现会从崭新的角度带来新的研究方法，因此我们将能更好的理解其发病原因，以及该针对哪些基因来设计治疗方法。”
??遗传性痉挛性截瘫是一种遗传性疾病，患者症状是下肢进行性萎缩和僵直，其中大多最终将瘫痪。和许多神经变性疾病一样，典型的病人从20岁到50岁之间开始出现病症，而随着时间推移症状进行性加重。由于没有彻底有效的治疗措施，医生只能采取一些物理疗法来改善肌肉力量和保持运动能力。
??杜克的研究人员发现其中一种遗传性痉挛性截瘫与REEP1基因有关。该基因通常编码支持细胞能量源泉—线粒体的蛋白质。但缺陷基因却不同产生蛋白质以维持线粒体的正常功能—尤其是神经系统细胞通路的线粒体。杜克人类基因学研究中心主任及该研究的负责人Margaret Pericak-Vance博士说，目前尚不清楚这类蛋白质究竟如何发生故障。
??杜克研究中心的科学家们研究了两个存在遗传性痉挛性截瘫患者的家庭。
??研究人员运用基因制图技术鉴定了2号染色体上的一小段DNA，而通常认为致病基因就存在于该染色体。研究人员还检测了9名志愿者的基因，这些基因在控制神经变性疾病的细胞通路上发挥着潜在的作用。研究人员仔细检查了这些基因的DNA顺序，并定位了遗传性痉挛性截瘫患者的REEP1基因突变。
??Pericak-Vance及同事 Allison Ashley-Koch博士说，遗传性痉挛性截瘫患者REEP1基因作用的发现更进一步证明了，线粒体功能的缺陷是许多神经变性疾病的原因。例如，科学家已经发现葛雷克氏症是由于SOD1基因突变，而该基因编码的蛋白质也在线粒体里表达。
??鉴于REEP1作用的发现，科学家们正设计一种基因检查来诊断存在该基因缺陷的病人，Züchner说道。杜克大学研究小组已经将其成果转让Athena 技术公司以开发相关基因检查。
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.
