Parietal lobe deficits in frontotemporal lobar degeneration caused by a mutation in the progranulin gene.
OBJECTIVE
To describe the clinical, neuropsychologic, and radiologic features of a family with a C31LfsX35 mutation in the progranulin gene CCDS11483.1).


METHODS
Case series.


METHODS
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.


CONCLUSIONS
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.
Rohrer
Jonathan D
JD
Dementia Research Centre, Institute of Neurology, University College London, London, England.
Warren
Jason D
JD
Omar
Rohani
R
Mead
Simon
S
Beck
Jonathan
J
Revesz
Tamas
T
Holton
Janice
J
Stevens
John M
JM
Al-Sarraj
Safa
S
Pickering-Brown
Stuart M
SM
Hardy
John
J
Fox
Nick C
NC
Collinge
John
J
Warrington
Elizabeth K
EK
Rossor
Martin N
MN
D000368:Aged; D001039:Aphasia, Broca / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D001072:Apraxias / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D001284:Atrophy; D003072:Cognition Disorders / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D004252:DNA Mutational Analysis; D003704:Dementia / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*; D018450:Disease Progression; D005260:Female; D005625:Frontal Lobe / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007859:Learning Disabilities / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D009042:Motivation; D009434:Neural Pathways / Q000503:physiopathology; D009483:Neuropsychological Tests; D010296:Parietal Lobe / Q000473:pathology / Q000503:physiopathology*; D010375:Pedigree; D010468:Perceptual Disorders / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D010641:Phenotype; D013702:Temporal Lobe / Q000473:pathology / Q000503:physiopathology; D014796:Visual Perception / Q000235:genetics