Genetic switch controls hereditary heart defect

Writing in the journal Developmental Cell this month, researchers led by Dr Anne Voss and Dr Tim Thomas at the Walter and Eliza Hall Institute in Australia reveal a genetic "switch" that might explain variations in how severely children are affected by an inherited heart condition called Di George syndrome, which affects roughly one in every 4,000 babies. The condition is caused by a fault in a specific region of human chromosome 22, and many of the symptoms are linked to loss of a gene in that region called Tbx1, although they can range from mild to severe. Even identical twins with the same mutation may have different conditions, suggesting than non-DNA factors are at work.

Using a mouse model of Di George syndrome, the researchers discovered that levels of a protein called MOZ control the levels of Tbx1, which in turn control how severe a child's symptoms are. MOZ is an enzyme that adds epigenetics marks to histones - the proteins that package DNA - so it acts independently of mutations in the underlying DNA sequence. Intriguingly, the researchers also found that defects were more severe in pups born to mothers whose diet was rich in vitamin A but also had low levels of MOZ. This research sheds light on the interactions between mutations, epigenetics and diet, helping to explain more about the complex factors that underlie birth defects.