Findings Show Mutations in Large Novel Gene, Hydin, May Cause Congenital Hydrocephalus

Congenital hydrocephalus, sometimes referred to as water on the brain, is characterized by an abnormal build up of cerebrospinal fluid (CSF) in the ventricles of the brain. A frequent birth defect occurring in 1 in every 1,000 live births, researchers are working to identify the cause of the condition. Researchers at Columbus Children's Research Institute (CCRI) on the campus of Columbus Children's Hospital have discovered a large novel gene that, when mutated, causes named congenital hydrocephalus in mice. The findings were presented May 6 during the 2003 Pediatric Academic Societies (PAS) annual meeting by Brian Davy, an Ohio State University graduate student in the laboratory of Michael Robinson, Ph.D., investigator, in the Center for Molecular and Human Genetics at CCRI.

"Because our data indicates this is the only gene disrupted in two types of hydrocephalic mice (hy3 and OVE 459), we have named this gene Hydin for hydrocephalus-inducing," said Dr. Robinson. "This gene is among the largest ever discovered. Hydin expression is found in the ependymal cells that line the ventricles within the brain. This is important because in humans the common clinical perspective is that communicating (non-obstructive) hydrocephalus is caused by blockage of CSF reabsorption. But Hydin is expressed at the site of production and flow, not reabsorption."

According to Dr. Robinson, Hydin is also expressed in the epithelial lining of lung bronchi and fallopian tubes as well as in developing sperm cells. These tissues all have something in common--cilia or flagella--whip-like appendages of cells that are used to move fluid or to propel the cells. "We haven't seen Hydin expressed anywhere that cilia are not present," said Dr. Robinson. "Yet, at this time no one knows why problems with cilia are linked to hydrocephalus, despite an association of cilia dysfunction and hydrocephalus in mice, rats, dogs and humans.

"Our findings are significant because the link between genetic human hydrocephalus and ependymal cell failure has not been appreciated or thoroughly investigated, but in mice ependymal cell failure seems to be the most common cause of hydrocephalus," added Dr. Robinson. "Future studies will focus on the biochemical role of Hydin and examine if human patients have mutations in Hydin as well as the role of ependymal cells in maintaining normal circulation of CSF."

About Hydrocephalus

Hydrocephalus can be congenital or acquired as the result of trauma or infection to the brain. More than 50 percent of hydrocephalus cases are congenital. Hydrocephalus occurs when CSF accumulates as a result of blockage or due to over production. CSF carries waste products away from tissues in and around the brain. Shunts are often used to redirect the CSF to another area of the brain, but there are a number of issues that can occur from treatment with shunts including obstruction and infection.

About Columbus Children's Hospital

Columbus Children's Hospital ranks among the top 10 in National Institutes of Health research awards and grants to freestanding children's hospitals in the country. With nearly 500,000 patient visits each year, Children's Hospital is a 111-year-old pediatric healthcare network treating newborns through age 21. In 2002, the Children's Research Institute conducted more than 250 research projects and is the home of the Center for Injury Research and Policy along with other Centers of Emphasis encompassing gene therapy; molecular and human genetics; vaccines and immunity; childhood cancer; cell and vascular biology; developmental pharmacology and toxicology; and biopathology. Pediatric Clinical Trials International (PCTI), a site management organization affiliated with the hospital, also coordinated more than 50 clinical trials. In addition to having one of the largest ambulatory programs in the country, Children's offers specialty programs and services. Each year, more than 75,000 consumers receive health and wellness education, and 2,000 students from 93 institutions and 500 residents receive training at Children's. More information on Children's Hospital of Columbus is available by calling (614) 722-KIDS (5437) or through the hospital's Web site at http://www.columbuschildrens.com.