Scientists have identified a gene mutation that causes two forms of cleft lip, according to an article in the October issue of Nature Genetics.
Studies have indicated that the relevant gene or genes for two cleft lip disorders—Van der Woude and popliteal pterygium syndromes—are in a region of chromosome 1. Finding the "causative" gene, however, has been difficult because there are many genes and single-nucleotide polymorphisms in the region.
To get around this problem, the researchers studied a set of identical twins, one of whom had a cleft lip while the other did not. As the twins were almost genetically identical, the scientists reasoned that comparing the twins’ DNA would show only one difference: the mutation causing the condition. Researchers identified a mutation in the gene encoding interferon regulatory factor 6, or IRF6, which produces a protein involved in turning other genes on and off and appears to play a key role in the formation of lips, palate, skin and genitalia.
To confirm their discovery, researchers studied 122 families who had one of the two syndromes. They identified mutations in IRF6 in 45 unrelated families affected by Van der Woude syndrome, as well as distinct mutations in 13 unrelated families affected with popliteal pterygium syndrome.
Researchers say that identifying IRF6 as a key determinant in orofacial development will help them further discover and integrate the molecular pathways responsible for the development of the lip and palate.
