Spina Bifida Gene Identified; Groundbreaking Research Can Make Diagnosis Easier

“We’ve known for years that there’s a genetic component, and now we’ve discovered one of the culprits,” said Dr. Philippe Gros, James McGill Professor of Biochemistry and Distinguished Scientist for the Canadian Institutes of Health Research (CIHR) at McGill.

Dr. Gros and his team of post-doctoral fellows collaborated with researchers at the Instituto G. Gaslini in Genoa, Italy, to study patients with neural-tube defects (NTDs). The team identified three mutations in the VANGL1 gene that implicate the gene as a risk factor in human NTDs. Their findings appear in the April issue of the New England Journal of Medicine.

“This is the first gene that has been shown to cause the disorder in humans,” said Dr. Gros, whose lab has been studying NTDs in mice for over a decade and was the first to clone the gene for laboratory study prior to the recent human trials.

NTDs are characterized by the incomplete closure of the embryonic neural tube, resulting in the incomplete development of the spine and spinal cord. Some types of the disorder, such as anencephaly, result in stillbirth or death very soon after delivery, while with spina bifida, survival rates are often longer despite severe disabilities including varying degrees of paralysis. After cardiac abnormalities, NTDs are the second most common birth defect, occurring in as many as two births in a thousand.

In addition to the genetic risk, there is a strong environmental component to the occurrence of NTDs. Folic-acid supplementation during pregnancy has been shown to reduce the incidence of neural-tube defects by 50 to 70 percent.

“This discovery won’t have a major impact on the search for a cure yet, but it can have an immediate impact on diagnosis or risk assessment,” noted Dr. Gros, whose lab is funded by the Canadian Institutes of Health Research. “A pre-natal diagnosis would allow physicians to decide whether to follow a pregnancy more closely.”

“Since NTDs constitute of the most prevalent types of serious birth defects, even after the reduction achieved with folic-acid fortification of grain products, these new research findings on the genetics and developmental mechanisms underlying neural-tube defects hold great promise for preventing future cases and their devastating consequences for children and families,” said Dr. Michael Kramer, Scientific Director of the CIHR Institute of Human Development, Child and Youth Health.