NEW YORK (Dispatches) -- University of Pittsburgh scientists have recently discovered that when a particular genetic mutation is induced in mouse eggs, the resulting embryos would all die in the womb within a week.
The researchers realized that a protective gene was countering the bad one, giving a reason for
why some people with this very deleterious gene not only survived but did so with only an atrial septal defect -- a hole in the heart.
The research team obtained genetic samples from eight members of a family who all had large atrial septal defect. Whole genome sequencing revealed that they all carried an extremely rare mutation in a gene called TPM1 that didn’t appear in more than 900 unrelated samples from people with congenital heart disease; worldwide, it has been seen only twice.
When the team introduced both the deleterious and protective mutations simultaneously in the mouse embryos, beating hearts were observed. Atrial septal defect still occurred, as seen in the family members with these two mutations. The protective gene wasn’t strong enough to completely overpower the damage caused by the bad one, but the heart could beat well enough to sustain life.
The discovery can have immediate implications for helping families understand the risk of passing the mutations to future generations, as well as help guide clinical treatment, such as prompting doctors to consider early treatments or more frequent assessments for heart dilation and rhythm disturbances. For example, with some heartbeat irregularities, surgically implanting a pacemaker or a defibrillator could be helpful in restoring normal heart beating.