This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Dementias  • Neurogenetics  • Neurology, Other  • Genetic Disorders  • Alert me on articles by topic  Social Bookmarking   What's this?

Jonathan D. Rohrer, MRCP; Jason D. Warren, PhD, FRACP; Rohani Omar, MRCP; Simon Mead, PhD; Jonathan Beck, BSc; Tamas Revesz, MD; Janice Holton, PhD; John M. Stevens, DRACR, FRCR; Safa Al-Sarraj, MSc, FRCPath; Stuart M. Pickering-Brown, PhD; John Hardy, PhD; Nick C. Fox, MD, FRCP; John Collinge, FRS; Elizabeth K. Warrington, FRS; Martin N. Rossor, MD, FRCP

Arch Neurol. 2008;65(4):506-513.

Objective  To describe the clinical, neuropsychologic, and radiologic features of a family with a C31LfsX35 mutation in the progranulin gene CCDS11483.1).

Design  Case series.

Patients  A large British kindred (DRC255) with a PGRN mutation was assessed. Affected individuals presented with a mean age of 57.8 years (range, 54-67 years) and a mean disease duration of 6.1 years (range, 2-11 years).

Results  All patients exhibited a clinical and radiologic phenotype compatible with frontotemporal lobar degeneration based on current consensus criteria. However, unlike sporadic frontotemporal lobar degeneration, parietal deficits, consisting of dyscalculia, visuoperceptual /visuospatial dysfunction, and/or limb apraxia, were a common feature, and brain imaging showed posterior extension of frontotemporal atrophy to involve the parietal lobes. Other common clinical features included language output impairment with either dynamic aphasia or nonfluent aphasia and a behavioral syndrome dominated by apathy.

Conclusion  We suggest that parietal deficits may be a prominent feature of PGRN mutations and that these deficits may be caused by disruption of frontoparietal functional pathways.

Author Affiliations : Dementia Research Centre (Drs Rohrer, Warren, Omar, Fox, Warrington, and Rossor), Medical Research Council Prion Unit, Department of Neurodegenerative Disease (Drs Mead and Collinge and Mr Beck), and Department of Molecular Neuroscience (Drs Revesz and Holton), Institute of Neurology, University College London, London, England; Department of Clinical Neuroradiology, National Hospital for Neurology and Neurosurgery, London (Dr Stevens); Department of Clinical Neuropathology, King's College Hospital, London (Dr Al-Sarraj); Division of Regenerative Medicine, Department of Medicine, University of Manchester, Manchester, England (Dr Pickering-Brown); and Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland (Dr Hardy).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

"Frontotemporoparietal" dementia: Clinical phenotype associated with the c.709-1G>A PGRN mutation
Moreno et al.
Neurology 2009;73:1367-1374.
ABSTRACT | FULL TEXT  

Voxel-based morphometry patterns of atrophy in FTLD with mutations in MAPT or PGRN
Whitwell et al.
Neurology 2009;72:813-820.
ABSTRACT | FULL TEXT