BOSTON ? Mutations in a recessive gene that causes early-onset Parkinson's disease also occur in about 12% of those whose families have a familial form of the disease, researchers here reported.
BOSTON, June 14 ? Mutations in a recessive gene that causes early-onset Parkinson's disease also occur in about 12% of those whose families have a familial form of the disease, according to researchers here.
And even carrying a mutation in one copy of the PARK2 gene significantly lowers the age of onset of Parkinson's disease, said to Mei Sun, M.D., Ph.D., of Massachusetts General Hospital and Harvard Medical School.
When both copies of the PARK2 gene are mutated, the gene product parkin is inactivated, resulting in early-onset Parkinson's, Dr. Sun and colleague reported in the June issue of the Archives of Neurology.
But although the mutations were presumed to be recessive, Dr. Sun and colleagues found, "there is increasing evidence suggesting that heterozygous mutations may confer increased susceptibility to late-onset Parkinson's."
As part of the GenePD study, the researchers analyzed the genomes of 183 families with at least two members with Parkinson's. Aside from having two affected members, the studied families also had to have had either affected siblings whose PARK2 genes were identical or at least one family member with an age of onset of younger than 54.
At least one member from each of the 183 families underwent comprehensive screening for mutations in PARK2, the researchers reported.
The genetic analysis found that 23 families (12.6%) had mutations in PARK2. Of those:
Having any mutation in PARK2 was associated with a mean age of onset of 42.9 years (with standard deviation of plus or minus 14.1 years.)
When the researchers looked at age of onset in the 91 families whose affected siblings had identical PARK2 alleles, they found three clusters: Patients with one mutation had an 11.7-year decrease in age at onset compared with patients with none, while patients with two or more mutations had a 13.2-year decrease in age at onset compared with patients with one.
Both differences were statistically significant at p