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【bio-news】对出生缺陷的研究可能产生新疗法
Research could lead to new treatments for birth defects
Pioneering new research into cleft lip and palate could open the door to babies with certain craniofacial disorders being successfully treated in the womb.
University of Manchester researchers have uncovered the causes behind two genetic conditions that lead to facial anomalies including clefts, where the lip and often the roof of the mouth, or palate, fail to form properly.
Working with colleagues at the University of Iowa, Manchester husband and wife team Mike and Jill Dixon together with researcher Rebecca Richardson, have identified the role of a gene called IRF6.
"We had previously shown that a mutation in the IRF6 gene causes Van der Woude syndrome ?a rare inherited form of cleft lip and palate," said Professor Mike Dixon, a dentist based in the Faculty of Life Sciences.
"It has also been found that defects in this gene are responsible for a significant number of other cleft lip and palate disorders that are not related to any particular syndrome."
The team established that mice missing the gene developed abnormal skin as well as cleft palate. Further analysis revealed that IRF6 controls the development of keratinocytes ?the main type of cells in the outer layers of the skin, known as the epidermis.
"Put simply, mutations of IRF6 in Van de Woude syndrome make the skin cells too sticky, so they stick to each other and other types of cell much sooner than they should resulting in these facial anomalies," said Professor Dixon.
The findings ?published in the journal Nature Genetics this week ?surprised the researchers, as all other genes in the IRF family have completely different roles, primarily in the body's immune response.
"This unexpected role for IRF6 in skin development may mean it is involved in other medically important areas of biology such as cancer and wound healing.
"In any event, this research has the potential to lead to new ways of treating cleft lip and palate caused by this genetic mutation, as targeting the defective gene during pregnancy could help the skin cells develop normally."
Further research by the Manchester team, this time with scientists at the Stowers Institute for Medical Research in Kansas, has uncovered the cellular processes involved in another genetic disorder that results in cleft palate.
Treacher Collins syndrome is characterised by underdeveloped jaw and cheek bones and ear anomalies, as well as cleft palate.
Whereas cleft lip and palate remains the most common form of congenital abnormality, affecting one in 1,000 babies in the UK, Treacher Collins syndrome is a relatively rare genetic disorder affecting one in 50,000 individuals.
"We identified the gene associated with this disorder some time ago but we have now established the reason for the anomalies," said Dr Jill Dixon.
"Working with a mouse model, we found that the craniofacial disorders are caused by the high number of cells, known as neural crest cells, that die before they have migrated to form the bone, cartilage and connective tissue in the face and head of the unborn animal.
"When translated to human development, this failure to produce enough neural crest cells in the first three to eight weeks of pregnancy results in the craniofacial anomalies observed in Treacher Collins syndrome."
Dr Paul Trainor, who headed the Kansas team, said the findings ?published in the Proceedings of the National Academy of Sciences (PNAS) ?were an exciting step in their investigations of genetic birth defects.
"In ongoing studies in the lab, we are testing a number of methods for chemically and genetically inhibiting the early period of cell death in an effort to stimulate the production of neural crest cells which could help to prevent the development of craniofacial anomalies."
Dr Robb Krumlauff, Scientific Director at the Stowers Institute, added: The results represent a major breakthrough in our understanding of Treacher Collins syndrome. But the door that these findings open ?to the possibility of intervening in utero to prevent the disease ?is truly groundbreaking."
### 认领此篇 认领的该篇已翻译完,请大家指导,翻译如下:
对出生缺陷的研究可能产生新疗法
该研究为先天缺陷的新的治疗方法。对于裂唇、裂鄂的新研究打开了子宫内成功治疗新生儿颅面部发育缺陷的大门。
曼彻斯特大学的研究者未能确定是哪两种遗传因子导致面部发育异常，包括裂唇、裂鄂及嘴唇发育不完整。在爱荷华州大学和曼彻斯特大学工作的Mike and Jill Dixon 夫妇和 Rebecca Richardson研究者已经确定了遗传因子IRF6的作用。
权威的牙科医生Mike Dixon教授说：“我们以前已经发现了IRF6遗传因子突变影起的唇鄂裂综合征。很少有通过遗传形成裂唇裂鄂。”现已发现与某些特殊综合征无关的裂唇、裂鄂的产生，是由于遗传因子的缺陷引起的。
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作者:admin@医学,生命科学 2011-07-29 05:15
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