Affiliations: [a] Neurorehabilitation Unit, Department of Clinical Neurosciences, Vita Salute University and San Raffaele Scientific Institute, Milan, Italy | [b] Department of Neurological Sciences, ‘Dino Ferrari’ Center, University of Milan, Fondazione Ca' Granda, IRCCS Osp. Maggiore Policlinico, Milan, Italy
Correspondence:
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Correspondence to: Dr. Chiara Cerami, Vita-Salute University and San Raffaele Scientific Institute, Department of Clinical Neurosciences, Neurorehabilitation Unit, Via Stamira D'Ancona, 20 - 20127 Milano, Italy. Tel.: 0039 02 2643 5730; Fax: 0039 02 2643 5738; E-mail: [email protected].
Abstract: Frontotemporal lobar degeneration (FTLD) is a common early-onset dementia, which shows highly heterogeneous phenotypic presentations. Although an autosomal dominant transmission can be found only in about 10% cases, familial aggregation is frequently observed in FTLD. Recently, the progranulin gene (GRN) was reported to be involved in the disease pathogenesis. We describe two clinically different, apparently sporadic FTLD cases, sharing the previously described GRN mutation g.11019_11022delCACT (relative to nt1, NCBI NG_007886.1), alias Thr272fs, with a premorbid psychiatric history. Both patients are males and were in their sixties when diagnosed clinically with, respectively, the behavioral variant of frontotemporal dementia (bvFTD) and progressive nonfluent aphasia (PNFA). In both cases, the medical history revealed the presence of bipolar spectrum disorders. Mutations in GRN are considered to be a major cause of FTLD. However, the phenotypes associated with these mutations are highly variable. Our description of two novel FTLD genetic cases confirms the high frequency of the g.11019_11022delCACT mutation in Northern Italy. On this basis, we recommend to consider the presence of this mutation as a possible cause of the disease, particularly in patients with premorbid psychiatric symptoms.
