Mosaicism in iris color not a problem — compared, say, to mosaicism in kidneys
When Meriel M. McEntagart, a geneticist at St. George’s University of London, met this family in May 2012, she suspected that three of the children had a rare genetic disorder called Smith-Magenis syndrome…Dr. McEntagart confirmed that diagnosis with a genetic test. The children were all missing an identical chunk of a gene known as RAI1.
One of the children had a different father from the other two, and so the mother could be the only source of their altered gene. But when Dr. McEntagart ran a standard blood test on the mother, the results were not nearly so straightforward: The woman had a normal version of RAI1.
Dr. McEntagart and her colleagues suspected that the answer to this puzzle was that the mother was a genetic mosaic.
We tend to think of ourselves as having just one set of genetic material, which exists in identical form in every one of our cells. But sometimes, people have two or more significantly different genomes. As our cells divide, some may go through a major mutation. So some individuals end up with groups of cells that have very different DNA from the rest of them.
Dr. McEntagart said that she suspected that the mother she encountered had a normal version of RAI1 in some cells but an altered version in other cells, including her eggs.
“We wanted to understand if there was a way to demonstrate that she was a mosaic,” Dr. McEntagart said…
In a study released Thursday in the American Journal of Human Genetics, the Baylor team and its colleagues describe the biggest search for cases in which mosaic parents passed down disease-causing mutations to their children. It turns out to be far from a fluke…
Michael Snyder, a geneticist at Stanford University who was not involved in the study, said it showed that mosaicism could have a significant effect on not just people’s own health, but on their children as well.
Having developed a method for detecting mosaic parents, the scientists decided to conduct a larger study to see how common mosaicism is. They began searching for families that would be willing to participate. Each family had to have a child that had a genetic disorder caused by the deletion of some DNA. And they had to have taken a standard genetic test that had failed to find the deletion in either parent’s genes.
Eventually, the scientists were able to study 100 families. They searched for cases in which the parents were mosaics and had the same mutation as their children.
“We thought going into this study we’d find maybe one or two if we were lucky,” said Ian M. Campbell, the lead author of the study. “And then we found four.”
Mr. Campbell and his colleagues were surprised to find that many mosaic parents. And they suspect that the true number of mosaics among the 100 families was even higher. For one thing, their method lets them detect only genetic deletions, but other kinds of mutations can cause genetic disorders, too.
James R. Lupski, another co-author on the study, points to a second limitation of the study. “It only tells you what you see in the blood,” he said. If the scientists could have examined muscle or other tissues, they might have found even more mosaic cells.
The results suggest that some people can have serious genetic diseases without any symptoms. That’s because they have the defective version of a gene in only some of their cells, and their other cells compensate for them.
But such people are unknowingly at risk of having children with full-blown versions of their diseases, if the mutation appears in their reproductive cells. Dr. Lupski said that as technology improved, clinical geneticists should test people for this hidden risk.
“Couples are going to want some answers,” he said.
Another benefit of modern science – unfortunately rejected by some. Equipping a happy couple to make an informed decision about whether or not to bring someone into life that may be one of unwarranted difficulty and pain is at a minimum an opportunity for choice.