Posted Dec 30, 2011
–Ohio State University researchers have found what they believe is the second-oldest-known genetic disease mutation.
The mutation causes a disorder known as Imerslund-Grasbeck syndrome, a rare and dangerous deficiency of vitamin B12.
The mutation is about 13,600 years old and originated in the Middle East, according to a research team led by Stephan M. Tanner, a researcher in the Comprehensive Cancer Center’s human cancer genetics program.
It is now seen in people of Arabic, Jewish and Turkish ancestry. More-recent genetic disease mutations of this type often are found within a single group, such as the Amish, Tanner said.
The discovery is remarkable for its historic value, but it also might play an important role in identifying the disease in people of certain ethnic backgrounds, said Tanner, an assistant professor of molecular virology, immunology and medical genetics.
The oldest-known genetic disease mutation is linked to cystic fibrosis and first showed up as long as 52,000 years ago.
The work of Tanner’s team started with genetic samples from an Israeli family and eventually included samples from 16 affected families.
Scientists used a complex analysis to estimate the age of the mutation, including looking at the size of the section of the chromosome on which the mutation appears. As a mutation is passed down through generations, the section on which it is located gets shorter.
Only about 500 cases of Imerslund-Grasbeck syndrome have been identified worldwide. But Tanner said it is unclear how common the disorder is because people might be treated for B12 deficiency even though no specific disorder has been diagnosed. There are many causes for the deficiency.
The syndrome can cause anemia, growth problems, increased risk of infection and impaired neurological development. It is a recessive disorder. That means, if a mother and father are both carriers, there’s a 25 percent chance the disorder will show up in each of their children.
Dr. John C. Fyfe, a veterinarian and associate professor of microbiology and molecular genetics at Michigan State University, said the research is important to genetic science in general.
More specifically, it could help the families affected by the disease, said Fyfe, who studies the disorder in dogs. A pediatrician assessing a B12 deficiency in a 2-year-old child of Turkish descent, for example, would have a strong clue what the diagnosis might be, he said.
Imerslund-Grasbeck syndrome was first identified 50 years ago. The mutation discovered by the Ohio State team is responsible for half of the cases in Arabic, Turkish and Jewish people and 15 percent of all cases that have been studied, Tanner said.
Commercially, a test for a specific mutation such as this might cost about $500, he said. Broader genetic testing to try to figure out what was causing the deficiency would run several thousand dollars.
Parents who know they’re carriers of the mutation can identify the syndrome more quickly when a child is born and begin monthly B12 shots, a relatively simple — and highly effective — treatment. Early treatment prevents more-severe, lingering neurological problems.
The research was published in the Orphanet Journal of Rare Diseases.
mcrane@dispatch.com
©2011 The Columbus Dispatch (Columbus, Ohio)
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