In a study published Thursday in the American Journal of Human Genetics , the MCG team and international contributors in Colombia, France, Spain, China, Ireland and England trace the cause of urofacial syndrome to defects in the heparanase 2 gene. The syndrome is characterized by grimacing when trying to smile or laugh, and a host of urinary problems, such as incontinence or retention of urine that can destroy the kidneys.
It was first reported by Dr. Bernardo Ochoa of Colombia in 1987, which is why it is sometimes called Ochoa syndrome, and has been documented only about 100 times worldwide, primarily in the Antioquia region of Colombia.
"In this particular area of Antioquia it is popular for first cousins to marry," said Bobbilynn Hawkins-Lee, professor of urology at MCG. Of the 19 families initially studied in that region, there were nine intermarriages, said Hawkins-Lee, who is also director of urodnynamics and female urology at the Charlie Norwood VA Medical Center in Augusta.
She first heard Ochoa speak in 1989 when she was a fellow in pediatric urology at the University of Florida and approached him about doing a genetic study of his urofacial families. She was later steered to Dr. Jin-Xiong She, who is now the director of the Center for Biotechnology and Genomic Medicine at MCG, and secured a small grant in 1994 to start.
"Fifteen years in the making," Dr. She joked.
Studying patients from Colombia, Spain and the United States, they were able to track down the gene, also known as HPSE2, and found its protein is prevalent in bladder and facial muscles but not much in skeletal muscles. While the two muscle systems would seem to be very different they are actually quite similar because they involved coordinated function of different muscles doing different things simultaneously, said Cong-Yi Wang, a molecular geneticist at MCG.
"Urination is a coordinated action," he said. "The facial muscle is the same. Some muscle has to be contracted and other muscle has to be relaxed at the same time to get normal facial expression."
The gene might produce a protein that regulates the control of these muscles. While the disease is rare, outside of the facial muscle part, it is similar to other bladder control problems, which are quite common and could affect 16-18 percent of the general population, Wang said.
"This is thus far the only genetic defect identified relative to voiding (urinating) disorders," he said.
The MCG researchers are looking at inducing the defect in mice to see if it can replicate the symptoms and whether mice that produce a lot of the protein are resistant to similar disorders. The researchers would like to study people who have bladder control problems to look for evidence of the genetic defect, Wang said.
It also opens itself to powerful drug screening tools Dr. She has, and that presents some great possibilities, Hawkins-Lee said.
"It's very exciting to us because that is exactly what we are aiming for eventually in these types of bladder abnormalities that are so common, (such as) overactive bladder," she said. "That would be one of our endpoints is to find medications that would control or improve the function of the bladder muscles."