Co-Occurrence of the C9ORF72 Expansion and a Novel GRN Mutation in a Family with Alternative Expression of Frontotemporal Dementia and Amyotrophic Lateral Sclerosis

Article type: Short Communication

Authors: Testi, Silvia^{a; 1} | Tamburin, Stefano^{b; 1} | Zanette, Giampietro^c | Fabrizi, Gian Maria^{a; *}

Affiliations: [a] Section of Neuropathology, Department of Neurological and Movement Sciences, University of Verona, Verona, Italy | [b] Section of Clinical Neurology, Department of Neurological and Movement Sciences, University of Verona, Verona, Italy | [c] Neurology Section, Pederzoli Hospital, Peschiera del Garda, Verona, Italy

Correspondence: [*] Correspondence to: Gian Maria Fabrizi, MD, PhD, Section of Neuropathology, Department of Neurological and Movement Sciences, University of Verona, Policlinico G.B. Rossi, P.le L.A. Scuro, 10, 37134 Verona, Italy. Tel.: +39 045 812 4461; Fax: +39 045 802 7492; E-mail: gianmaria.fabrizi@univr.it.

Note: [1] These authors contributed equally to this work.

Abstract: The C9ORF72 repeat expansion is the major cause of frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), and FTLD-ALS. In the reported pedigree, the 47-year old proband, presenting a four-year history of frontotemporal dementia, carried the C9ORF72 expansion plus a novel GRN p.Cys246X mutation. The father and a paternal uncle, harboring the C9ORF72 expansion only, had died by pure ALS with onset at 63 and 76 years, respectively. The case report and a review of the literature emphasize that phenotypical variations of the FTLD-ALS spectrum could be due to digenic inheritance.

Keywords: Amyotrophic lateral sclerosis (ALS), C9ORF72, frontotemporal lobar degeneration (FTLD), FTLD-ALS, GRN

DOI: 10.3233/JAD-141794

Journal: Journal of Alzheimer's Disease, vol. 44, no. 1, pp. 49-56, 2015