A USC research team has pinpointed the source
of a genetic disorder that causes life-threatening birth
defects, which may allow doctors to quickly diagnose
and better treat the disease.
Babies born with the disorder, known as Loeys-
Dietz syndrome or Marfan syndrome type II, have
cleft palates and other facial characteristics similar to
babies born with other diseases–but also happen to
suffer potentially fatal heart defects, making it critical
for them to receive an accurate diagnosis right away.
Researchers from USC found an abnormally high
amount of a protein known as Transforming Growth
Factor Beta (TGF-ß) outside of cells–which may be
revealed by a blood or tissue test–in patients with
characteristic facial defects is a key indicator of
“If we can screen patients for this, it can identify
Loeys-Dietz syndrome and inform clinical practice,”
said Yang Chai, director for the USC Center for
Craniofacial Molecular Biology and corresponding
author of the study. “And perhaps, one day we can
manipulate the amount [of TGF-ß] and possibly rescue
the cleft palate before a baby is born. The
prospects of this are very promising.”
Led by senior postdoctoral fellow Junichi Iwata of
the Ostrow School of Dentistry at USC, researchers
made their discovery by studying the fetal development
of mice. They found that mutations that affect
the way TGF-ß communicates outside of a cell may
cause Loeys-Dietz syndrome.
TGF-ß controls many of the functions within a
cell, and is known to be heavily involved in the
palate’s formation–or failure to form. Typically, it
uses a receptor protein known as TGFBR2 to communicate
outside of the cell. However, if a mutation
causes a roadblock on that communication highway,
TGF-ß may rely on surface streets to get its signal
out. In clinical studies, the activation of this separate
signaling pathway resulted in palate and facial defects
akin to Loeys-Dietz syndrome. A tell-tale sign of the
alternate pathway’s activity is an abnormally high
amount of TGF-ß outside of the cell.
Also, additional genetic defects in the alternate
pathway led to a disruption in its signaling, which
lowered the amount of TGF-ß outside of the cell and
rescued the palate and facial deformities, essentially
correcting the defects before birth with no other
Their work was published in the Journal of
Clinical Investigation. Funding for this research came
from the National Institute of Dental and
Craniofacial Research, the National Institutes of