From genotype to phenotype: Two cases of genetic frontotemporal lobar degeneration with premorbid bipolar disorder

Chiara Cerami, Alessandra Marcone, Daniela Galimberti, Chiara Villa, Elio Scarpini, Stefano F. Cappa

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)791-797
Number of pages7
JournalJournal of Alzheimer's Disease
Issue number4
Publication statusPublished - 2011


  • Bipolar disorder
  • dementia
  • frontotemporal dementia
  • frontotemporal lobar degeneration
  • GRN mutation
  • primary progressive nonfluent aphasia

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Clinical Psychology


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