title: From genotype to phenotype: two cases of genetic frontotemporal lobar degeneration with premorbid bipolar disorder.
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.
authors: Neurorehabilitation Unit, Department of Clinical Neurosciences, Vita Salute University and San Raffaele Scientific Institute, Milan, Italy. cerami.chiara@hsr.it
authors: Chiara
authors: C
authors: Cerami
authors: Alessandra
authors: A
authors: Marcone
authors: Daniela
authors: D
authors: Galimberti
authors: Chiara
authors: C
authors: Villa
authors: Elio
authors: E
authors: Scarpini
authors: Stefano F
authors: SF
authors: Cappa
mesh_terms: D000328:Adult; D000368:Aged; D001714:Bipolar Disorder / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D001921:Brain / Q000473:pathology; D004252:DNA Mutational Analysis; D057174:Frontotemporal Lobar Degeneration / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D005838:Genotype; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D007558:Italy; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D000077153:Progranulins
chemical_list: C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins