NR AWIN
AU Ladogana,A.; Puopulo,M.; Poleggi,A.; Giannattasio,C.; Mellina,V.; Almonti,S.; Ingrosso,L.; Pocchiari,M.
TI Genetic anticipation in E200K Italian patients of the Calabrian cluster
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions GEN-16
PT Konferenz-Poster
AB
The genetic forms of Transmissible Spongiform Encephalopathies (TSEs) or prion diseases represent about 10-15% of human TSEs. Genetic TSEs are always associated with a mutation in the prion protein gene (PRNP), and occur in families with an autosomal dominant pattern of inheritance. However, the observations that they occasionally occur in families with no previous history of disease and that some PRNP mutant carriers do not develop disease during their lifetime raise the issue of factors influencing the penetrance and the age at onset of these diseases. Genetic anticipation has been shown in several neurodegenerative diseases where the gene linked to the disease is affected by trinucleotide repeat instability, with expansion of repeats clearly correlated with an earlier age at onset.
Preliminary evidence has shown anticipation in genetic CJD linked to the E200K mutation among Lybian Jews (Rosenmann H. et al 1999). The term anticipation in genetic disease refers to earlier age at onset and /or increased severity in successive generations.
We investigated whether genetic anticipation may occur in E200K Italian patients of the Calabrian cluster. We recorded the age at onset of 28 parent-offspring pairs from 22 pedigrees. When the parent at risk was alive and neurologically healthy we recorded the time at observation as the age at CJD onset. The paired t-test was performed to test the statistical significance of paired differences.
The age at onset for the carrier generation was 70.55 ± 11.5, while the age at onset of CJD offsprings was 58.8 ±10.7. The differences between the age at onset in the two generations was statistically significant (p< 0.0001). This result suggests that anticipation is also present in the Calabrian cluster of E200K cases. The basis for the anticipation in genetic E200K CJD is unknown. A number of genetic and environmental factors might play a role in determining the anticipation phenomenon.
AD Department of Cellular Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy. E-mail: ladogana@iss.it
SP englisch
PO Italien