Researchers report they now can predict whether some
parents are more likely than others to have a second child
with the “isolated” form of cleft lip and palate, one of
the world’s most common birth defects, according to results
of a study published in the “New England Journal
of Medicine”.
The research was supported in part by the
National Institute of Dental and Craniofacial Research and
the National Institute of Environmental Health Sciences,
part of the National Institutes of Health.
The authors say their latest gene test applies to about 12
percent of isolated cleft lip and palate, or babies born
with clefts only and no other birth defects. Last year, the
authors and their colleagues reported that mutations in
another gene account for about 2 percent of all cases of
isolated clefts, meaning researchers in the field now can
collectively screen for about 15 percent of isolated cleft
lip and palate, an impossibility just a few years ago.
Isolated clefts account for 70 percent of all cleft lip and
palate.
In the latest paper, the scientists report a so-called
“haplotype” gene test, one of the first of its kind in
medicine. A haplotype is the sum of several recurring
variations in the usual DNA sequence of a species that are
spaced out, like signposts, along a gene or chromosome. In
this case, they found that distinct combinations of
sequence variations in and around the gene IRF6 correlated
with an increased chance that a child would be born with a
cleft. IRF6, which encodes a gene-activating protein called
a transcription factor, plays a role during development in
orchestrating the normal formation of the lips, palate,
skin, and genitalia.
“This study shows that we’ve reached a point where it’s
possible to take blood samples from parents, test certain
genes, and determine whether their risk for a second child
with cleft lip or palate is, say, 1 or 20 percent,” said
Jeffrey Murray, M. D., a scientist at the University of
Iowa and the senior author on the study. “Now is the time
to begin thinking about how best to apply these types of
tests clinically and ensure that they truly benefit the
families and their children.”