Researchers have identified a new gene mutation linked to frontotemporal dementia, according to a study published in the Neurology.

Frontotemporal dementia, one form of which is known as Pick’s disease, involves progressive shrinking of the areas of the brain that control behavior and language. Symptoms include language problems and personality changes, often with inappropriate social behavior.
Unlike Alzheimer’s disease dementia, the disease does not affect memory in the early stages.
The genetic form of the disease is rare; most cases occur randomly.

The researchers discovered a new mutation in the gene named progranulin in an extended family in southern Italy. The genealogy of this family has been reconstructed for 15 generations, going back to the 16th century; 36 family members have had frontotemporal dementia. For this study, DNA tests were conducted on 70 family members, including 13 people with the disease.

. The mutation identified in this study is in a gene on chromosome 17. The mutation leads to a loss of progranulin, a protein growth factor that helps brain cells survive. The mutation causes only half of the protein to be produced, because only one copy of the gene is active. Production of too much progranulin has been associated with cancer.

The new gene mutation was found in nine of those family members with the disease and 10 people who are currently too young to have the symptoms of the disease. But four people with the disease did not have the gene mutation.
Amalia Bruni, of the Regional Neurogenetic Centre in Lamezia Terme, Italy, noted that these four people belong to a branch of the family with the disease in at least three generations. “ These results are intriguing, since the family has two genetically distinct diseases that appear almost identical,” said Bruni.

The Italian family had no cases with two copies of the mutated gene. “ We would have expected to see cases with two copies of the mutated gene, especially since this family shares much of the same genetic material, as there have been at least five marriages between first cousins over the years,” Bruni said. “ It’s possible that loss of both copies of the progranulin gene leads to the death of embryos, and that’s why there were no cases with two copies of the mutated gene.”

“Another intriguing aspect in this Italian family is the variable age at onset, which ranged from 35 to 87 years in the family members who inherited the same mutation.

Source: American Academy of Neurology, 2007

XagenaMedicine2007


Link: Xapedia - Medical Encyclopedia