Single gene causes cleft lip and palate

The cause of cleft lip and palate has always been a complex and unresolved issue. Now, in an international collaboration, scientists at Sydney’s Children’s Medical Research Institute (CMRI) have made a major contribution to understanding of the mystery of this condition.

Their breakthrough paper has been published in the current edition of the top scientific journal Nature Genetics.

Previous studies on cleft lip and palate suggested it is a so-called ‘multifactorial birth defect’ implying that several genes, plus environmental factors, cause the condition in babies during development.

Working with scientists from Canada and other countries, the CMRI lab have shown that a defect in a single gene, (Pdgfc), the C-form of the Platelet derived growth factor (PDGF) can cause the condition in mice.

“This is the first demonstration that losing the function of this one gene can cause cleft palate,” said Dr Patrick Tam, Head of the Embryology Unit at CMRI.

The pdgfc gene was discovered four years ago - at the Mount Sinai Hospital and University of Toronto in Canada, headed by Dr Nagy, however nothing was known about where and when it had its effects in development.

This is when the Canadians teamed up with Dr Patrick Tam’s laboratory to start finding answers. “Our laboratory has the expertise in looking at gene expression patterns, that is where and when genes are active,” said Dr Tam.

Removing the gene caused a cluster of abnormalities in the mouse embryos including spina bifida and changes to the skin. But the most significant finding was that in nearly 100% of the embryos there was a very clear cleft palate.

Several gene pathways had previously been suspected as the cause. “All of the other four genes previously found to have an association with cleft palate are unaffected by the loss of PDGF-C, indicating that PDGF-C is acting alone, not via the other known pathways.”