To breathe normally, people need more than just healthy lungs. A diaphragm - the large muscle that creates a vacuum to draw air into their lungs - is also crucial.
Birth defects in the diaphragm, such as congenital diaphragmatic hernia (which are about as common as cystic fibrosis), are often fatal. "A lot of people haven't heard of this [disorder] because so many of the kids die early," said Kate Ackerman, Harvard Medical School researcher and lead author of the study in the open access journal PLoS Genetics.
To explore the genetic roots of these birth defects - hitherto a mystery - Ackerman and her colleagues screened mice with induced genetic mutations. The researchers discovered that a mutation in the mouse Fog2 gene can cause small lungs and abnormal diaphragm development. Could the same gene be involved in human diaphragmatic defects? After studying children with similar problems, the authors did indeed identify a child with a serious Fog2 gene mutation who died on the first day of life with severe breathing difficulties, small lungs, and an abnormal diaphragm.
"This is the first identified cause of [this type of] diaphragmatic defect," Ackerman said. "And now we have a mouse model to try to learn more." This discovery means that researchers now have an important genetic starting point to generate further insight into a poorly understood range of human disorders.