PSEN1 and PRNP Gene Mutations Co-occurrence Makes Onset Very Early in a Family with FTD Phenotype

Article type: Short Communication

Authors: Bernardi, Livia^a | Anfossi, Maria^a | Gallo, Maura^a | Geracitano, Silvana^a | Colao, Rosanna^a | Puccio, Gianfranco^a | Curcio, Sabrina A.M.^a | Frangipane, Francesca^a | Mirabelli, Maria^a | Clodomiro, Alessandra^a | Di Lorenzo, Raffaele^a | Smirne, Nicoletta^a | Maletta, Raffaele^a | Iapaolo, David^b | Bruni, Amalia C.^{a; *}

Affiliations: [a] Regional Neurogenetic Centre, AS6 Lamezia Terme (CZ), Italy | [b] Neurogenetics Unit, IRCCS Neuromed, Pozzilli (IS), Italy

Correspondence: [*] Correspondence to: Dr. A.C. Bruni, Centro Regionale di Neurogenetica, ASP Catanzaro Viale A. Perugini, 88046 Lamezia Terme (CZ), Italy. Tel.: +39 0968 208080; Fax: +39 0968 208032; E-mail: bruni@arn.it.

Abstract: Prion protein (PRNP) gene mutations have recently been associated with clinical pictures resembling Frontotemporal dementia (FTD). We describe a novel seven extra-repeat insertional mutation in the PRNP gene in a family affected by early-onset autosomal dominant FTD previously reported as caused by a PSEN1 mutation in which there was inconsistency between clinical picture and genotype. Both mutations were pathogenic and showed a variable penetrance when present separately; when occurring together, the onset was very early, within the third decade of life. Genetic screening of the PRNP gene becomes of major importance in early onset autosomal dominant dementia.

Keywords: Frontotemporal dementia, genetic polymorphism, penetrance, presenilin-1, prion protein

DOI: 10.3233/JAD-2011-101890

Journal: Journal of Alzheimer's Disease, vol. 24, no. 3, pp. 415-419, 2011