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Gene behind cleft lip and palate identified
Scientists at University of Manchester have uncovered causes behind two genetic conditions that lead to facial anomalies such as clefts lip and palate, during birth.

Washington, Oct. 16 : Scientists at University of Manchester have uncovered causes behind two genetic conditions that lead to facial anomalies such as clefts lip and palate, during birth.

Working with colleagues at the University of Iowa, husband-wife team of Mike and Jill Dixon 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," he added.

The researchers found that mice without IRF6 developed abnormal skin as well as cleft palate. On conducting further analysis, they found that this gene 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.

"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," he added.

By conducting further research with scientists at the Stowers Institute for Medical Research in Kansas, the researchers uncovered the cellular processes involved in Treacher Collins, a syndrome is characterised by underdeveloped jaw, cheek bones, ear anomalies, and cleft palate.

While cleft lip and palate remains the most common form of congenital abnormality, Treacher Collins syndrome.

"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," she added.

The scientists are now conducting laboratory tests on 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 can help to prevent the development of craniofacial anomalies.

The study has been published in the Proceedings of the National Academy of Sciences (PNAS).

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