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Parietal Lobe Deficits in Frontotemporal Lobar Degeneration Caused by a Mutation in the Progranulin Gene
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).
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