Novel progranulin mutation: Screening for PGRN mutations in a Portuguese series of FTD/CBS cases

Mutations in the progranulin (PGRN) gene were recently described as the cause of ubiquitin positive frontotemporal dementia (FTD) in many families. Different frequencies of these genetic changes have been reported in diverse populations leading us to determine if these mutations were a major cause of FTD in the Portuguese population. The entire coding sequence plus exon 0 of PGRN were sequenced in a consecutive series of 46 FTD/CBS Portuguese patients. Two mutations were found: a novel pathogenic insertion (p.Gln300GlnfsX61) and a previously described point variant (p.T182M) of unclear pathogenicity. Pathogenic mutations in the PGRN gene were found in one of the 36 probands studied (3% of the probands in our series) who had a corticobasal syndrome presentation, indicating that in the Portuguese population, mutations in this gene are not a major cause of FTD. © 2008 Movement Disorder Society

[1]  T. Meitinger,et al.  A novel deletion in progranulin gene is associated with FTDP-17 and CBS , 2008, Neurobiology of Aging.

[2]  J. Trojanowski,et al.  Clinical, genetic, and pathologic characteristics of patients with frontotemporal dementia and progranulin mutations. , 2007, Archives of neurology.

[3]  J. Molinuevo,et al.  Late-onset frontotemporal dementia associated with a novel PGRN mutation , 2007, Journal of neural transmission.

[4]  K. Sleegers,et al.  Mutations other than null mutations producing a pathogenic loss of progranulin in frontotemporal dementia , 2007, Human mutation.

[5]  P. Heutink,et al.  Progranulin mutations in Dutch familial frontotemporal lobar degeneration , 2007, European Journal of Human Genetics.

[6]  Murray Grossman,et al.  TDP-43-Positive White Matter Pathology in Frontotemporal Lobar Degeneration With Ubiquitin-Positive Inclusions , 2007, Journal of neuropathology and experimental neurology.

[7]  R. Petersen,et al.  Neuropathologic Features of Frontotemporal Lobar Degeneration With Ubiquitin-Positive Inclusions With Progranulin Gene (PGRN) Mutations , 2007, Journal of neuropathology and experimental neurology.

[8]  J. Hardy,et al.  Progranulin mutations and amyotrophic lateral sclerosis or amyotrophic lateral sclerosis–frontotemporal dementia phenotypes , 2006, Journal of Neurology, Neurosurgery & Psychiatry.

[9]  J. Hardy,et al.  Progranulin mutations and ALS or ALS-FTD phenotypes , 2007 .

[10]  C. van Broeckhoven,et al.  Progranulin mutations in ubiquitin-positive frontotemporal dementia linked to chromosome 17q21. , 2006, Current Alzheimer research.

[11]  Michel Goedert,et al.  Frontotemporal lobar degeneration through loss of progranulin function. , 2006, Brain : a journal of neurology.

[12]  H. Feldman,et al.  The neuropathology of frontotemporal lobar degeneration caused by mutations in the progranulin gene. , 2006, Brain : a journal of neurology.

[13]  J. Hardy,et al.  Novel splicing mutation in the progranulin gene causing familial corticobasal syndrome. , 2006, Brain : a journal of neurology.

[14]  S. Melquist,et al.  Mutations in progranulin are a major cause of ubiquitin-positive frontotemporal lobar degeneration. , 2006, Human molecular genetics.

[15]  J. Trojanowski,et al.  Pathological heterogeneity of frontotemporal lobar degeneration with ubiquitin-positive inclusions delineated by ubiquitin immunohistochemistry and novel monoclonal antibodies. , 2006, The American journal of pathology.

[16]  Julie S. Snowden,et al.  Heterogeneity of ubiquitin pathology in frontotemporal lobar degeneration: classification and relation to clinical phenotype , 2006, Acta Neuropathologica.

[17]  C. Duijn,et al.  Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21 , 2006, Nature.

[18]  S. Melquist,et al.  Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17 , 2006, Nature.

[19]  A. Godbolt,et al.  Frontotemporal lobar degeneration with ubiquitin-only-immunoreactive neuronal changes: broadening the clinical picture to include progressive supranuclear palsy. , 2004, Brain : a journal of neurology.

[20]  M N Rossor,et al.  Frontotemporal lobar degeneration and ubiquitin immunohistochemistry , 2004, Neuropathology and applied neurobiology.

[21]  R. Faber,et al.  Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. , 1999, Neurology.

[22]  A. Lang,et al.  Motor neuron disease‐inclusion dementia presenting as cortical‐basal ganglionic degeneration , 1999, Movement disorders : official journal of the Movement Disorder Society.

[23]  M. Freedman,et al.  Frontotemporal lobar degeneration , 1998, Neurology.

[24]  Clinical and neuropathological criteria for frontotemporal dementia. The Lund and Manchester Groups. , 1994, Journal of neurology, neurosurgery, and psychiatry.