NR AXQS
AU Ladogana,A.; Puopolo,M.; Poleggi,A.; Giannattasio,C.; Nocentini,S.; Mellina,V.; Almonti,S.
TI Genetic Anticipation in v210i CJD Italian Patients
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Epidemiology, Risk Assessment and Transmission P04.116
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
Genetic Creutzfeldt-Jakob disease(CJD) is a rapidly progressive neurodegenerative disorder that typically affects individuals between the ages of 50-70 years. Five to fifteen percent of CJD cases show a familial pattern corresponding to autosomal dominant inheritance. Over 30 different point and insert mutations responsible for genetic CJD have been identified in the human PRNP gene. The V210I point mutation is the most common mutation in Italy accounting for more than 41% of the genetic TSE cases (Ladogana et al 2005). 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 same analysis, performed in E200K Italian patients of the Calabrian cluster, has shown a significant difference between the age at onset in two generations (Ladogana et al Abstract GEG-16 In "Prion 2006 Strategies, advances and trends towards protection of society" 3-6 October 2006 Torino Italy). We investigated whether genetic anticipation may occur in V210I Italian patients from the Southern Italy. We recorded the age at onset of 46 parent-offspring pairs from 34 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 69.35±11.74, while the age at onset of CJD offsprings was 57.5±9.7. 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 V210I Italian cases. The basis for the anticipation in genetic CJD is unknown. A number of genetic and environmental factors might play a role in determining the anticipation phenomenon.
AD A. Ladogana, M. Puopolo, A. Poleggi, C. Giannattasio, S. Nocentini, V. Mellina, S. Almonti, Istituto Superiore di Sanità, Cellular Biology and Neurosciences, Italy
SP englisch
PO Schottland