A gene called TFAP2A (Activating Enhancer-Binding Protein), has been linked to Branchio-Oculo-Facial syndrome (BOFS)by scientists at Boston University School of Medicine (BUSM). BOFS is characterized by frequent cleft lip and palate.
The team discovered that deletions or mutations within the TFAP2A gene cause distinctive clefting disorder Branchio-Oculo-Facial syndrome (BOFS), characterised by specific skin anomalies involving the neck and behind the ear, eye abnormalities, a typical facial appearance, and frequently cleft lip and palate.
In the study, led by Jeff Milunsky, MD, director of clinical genetics, associate director of the Center for Human Genetics, and an associate professor of pediatrics, genetics and genomics at BUSM, the researchers made use of the latest in molecular microarray technologies.
Using this, they examined one affected mother and son and two sporadic BOFS cases and found a small deletion on chromosome 6 in the mother and son.
After sequencing the genes in this candidate region, it was revealed that missense mutations accumulated in a particular region of the DNA-binding region of the TFAP2A gene in 4 sporadic BOFS patients.
Milunsky said that this discovery would lead to more precise diagnostic testing, enable prenatal diagnosis, suggest directions for new research, and facilitate genetic counseling in these families.
"This gene is a well-known transcription factor involved in multiple developmental pathways as well as tumorigenesis. An intriguing finding is that one of the affected patients with a mutation also has brain cancer, highlighting again the connection between malformations and cancer," he added.
He hopes that this discovery will have significant wide-ranging implications as this gene may also play a role in the more common isolated occurrence of cleft lip and palate.
The study currently appears on-line in a recent issue of the American Journal of Human Genetics.