Affiliations: [a] Department of Clinical Genetics, Helsinki University Central Hospital and Department of Medical Genetics, University of Helsinki, Helsinki, Finland
| [b] Department of Medical Biochemistry and Genetics, Institute of Biomedicine, University of Turku, and Tyks Microbiology and Genetics, Department of Medical Genetics, Turku University Hospital, Turku, Finland
| [c] Department of Pathology, Kuopio University Hospital, Kuopio, Finland
| [d] Department of Neurology, Helsinki University Hospital, and Molecular Neurology, Research Programs Unit, Biomedicum, University of Helsinki, Helsinki, Finland
| [e] Department of Pathology, University of Helsinki and HUSLAB, Helsinki, Finland
Correspondence:
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Correspondence to: Liisa Myllykangas, Department of Pathology, University of Helsinki and HUSLAB, Helsinki, Finland. Tel.: +358 504482805; Fax: +358 294126700; E-mail: [email protected].
Abstract: Mutations in the progranulin (GRN) gene represent about 5–10% of frontotemporal lobar degeneration (FTLD). We describe a proband with a novel GRN mutation c.687T>A, p.(Tyr229*), presenting with dyspraxia, dysgraphia, and dysphasia at the age of 60 and a very severe FTLD neuropathological phenotype with TDP43 inclusions. The nephew of the proband had signs of dementia and personality changes at the age of 60 and showed similar but milder FTLD pathology. Three other family members had had early-onset dementia. Gene expression studies showed decreased GRN gene expression in mutation carriers’ blood samples. In conclusion, we describe a novel GRN, p.(Tyr229*) mutation, resulting in haploinsufficiency of GRN and a severe neuropathologic FTLD phenotype.
