HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Correspondence: Submit a response Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rossi, G. Articles by Tagliavini, F. Search for Related Content PubMed PubMed Citation Articles by Rossi, G. Articles by Tagliavini, F.

Creutzfeldt–Jakob disease with a novel four extra-repeat insertional mutation in the PrP gene

From the Istituto Nazionale Neurologico Carlo Besta (Drs. Rossi, Giaccone, Giampaolo, Iussich, Puoti, Bugiani, and Tagliavini), Milan; and Clinica Neurologica, Università di Milano "Bicocca," Ospedale San Gerardo (Drs. Frigo, Cavaletti, and Frattola), Monza, Italy.

Address correspondence and reprint requests to Dr. Fabrizio Tagliavini, Istituto Nazionale Neurologico Carlo Besta, via Celoria 11, 20133 Milan, Italy; e-mail: ftagliavini{at}istituto-besta.it

OBJECTIVE: To investigate the role of a short insertional mutation in the prion protein (PrP) gene (PRNP) in prion disease pathogenesis.

BACKGROUND: The genetic forms of Creutzfeldt–Jakob disease (CJD) are associated with point or insertional mutations in PRNP. Whereas patients with five, six, seven, eight, and nine extra octapeptide repeats show an autosomal dominant pattern of inheritance and features of CJD, Gerstmann–Sträussler–Scheinker disease, or atypical dementia, patients with one, two, or four extra repeats have typical CJD and lack a family history of neurologic disorder.

METHODS: A genetic, neuropathologic, and biochemical study was carried out in a 65-year-old patient with clinical features of sporadic CJD.

RESULTS: A novel four extra-repeat insertional mutation of PRNP was found in the patient and in his 59-year-old healthy sister. The patient showed spongiosis, nerve cell loss, and gliosis associated with diffuse PrP immunoreactivity in the cerebral cortex, subcortical gray structures, and cerebellum. A peculiar aspect was the presence of focal PrP deposits in the basal ganglia and hypothalamus, superimposed to diffuse PrP immunoreactivity. The biochemical analysis revealed that both mutant and wild-type PrP participated in the pathologic process, and that the protease-resistant core of the altered PrP isoforms was distinct from that observed in sporadic, acquired, and other genetic forms of CJD.

CONCLUSION: These findings support the view that the four extra-repeat insertion in PRNP is a pathogenic mutation with low penetrance rather than a benign polymorphism, and suggest that this mutation results in the formation of a distinct PrP conformer.

This article has been cited by other articles:

				G Giaccone, G. Di Fede, M. Mangieri, L. Limido, R. Capobianco, S. Suardi, M. Grisoli, S. Binelli, P. Fociani, O. Bugiani, et al. A novel phenotype of sporadic Creutzfeldt-Jakob disease BMJ Case Reports, February 2, 2009; 2009(jan27_1): bcr0920080945 - bcr0920080945. [Abstract] [Full Text]

				C Mauro, G Giaccone, G Piscosquito, A Lavorgna, M Nigro, G Di Fede, A Leonardi, C Coppola, S Formisano, F Tagliavini, et al. A novel insertional mutation in the prion protein gene: clinical and bio-molecular findings J. Neurol. Neurosurg. Psychiatry, December 1, 2008; 79(12): 1395 - 1398. [Abstract] [Full Text] [PDF]

				G Giaccone, G Di Fede, M Mangieri, L Limido, R Capobianco, S Suardi, M Grisoli, S Binelli, P Fociani, O Bugiani, et al. A novel phenotype of sporadic Creutzfeldt Jakob disease J. Neurol. Neurosurg. Psychiatry, December 1, 2007; 78(12): 1379 - 1382. [Abstract] [Full Text] [PDF]

				A. Ladogana, M. Puopolo, A. Poleggi, S. Almonti, V. Mellina, M. Equestre, and M. Pocchiari High incidence of genetic human transmissible spongiform encephalopathies in Italy Neurology, May 10, 2005; 64(9): 1592 - 1597. [Abstract] [Full Text] [PDF]

				E A Croes, J Theuns, J J Houwing-Duistermaat, B Dermaut, K Sleegers, G Roks, M Van den Broeck, B van Harten, J C van Swieten, M Cruts, et al. Octapeptide repeat insertions in the prion protein gene and early onset dementia J. Neurol. Neurosurg. Psychiatry, August 1, 2004; 75(8): 1166 - 1170. [Abstract] [Full Text] [PDF]

				V. Pietrini, G. Puoti, L. Limido, G. Rossi, G. Di Fede, G. Giaccone, M. Mangieri, F. Tedeschi, A. Bondavalli, D. Mancia, et al. Creutzfeldt-Jakob disease with a novel extra-repeat insertional mutation in the PRNP gene Neurology, November 11, 2003; 61(9): 1288 - 1291. [Abstract] [Full Text] [PDF]

				C Yanagihara, M Yasuda, K Maeda, K Miyoshi, and Y Nishimura Rapidly progressive dementia syndrome associated with a novel four extra repeat mutation in the prion protein gene J. Neurol. Neurosurg. Psychiatry, June 1, 2002; 72(6): 788 - 791. [Abstract] [Full Text] [PDF]