Brain Advance Access originally published online on October 9, 2006
Brain 2006 129(11):3115-3123; doi:10.1093/brain/awl276
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Novel splicing mutation in the progranulin gene causing familial corticobasal syndrome
1 Linda C. Campbell Cognitive Neurology Research Unit, Sunnybrook Health Sciences Centre Toronto, Canada 2 Department of Medicine, Division of Neurology Toronto, Canada 3 Centre for Research in Neurodegenerative Diseases, Department of Medicine Toronto, Canada 4 Toronto Western Hospital Research Institute, University Health Network Toronto, Canada 5 Department of Pathology, Sunnybrook Health Sciences Centre, University of Toronto Toronto, Canada 6 Genetics Program, North York General Hospital Toronto, Canada 7 Laboratory of Neurogenetics, National Institute on Aging Bethesda, MD 8 Department of Pathology, University at Buffalo, State University of New York Buffalo, NY, USA
Correspondence to: Dr Sandra E. Black, Department of Medicine, Division of Neurology, Sunnybrook Health Sciences Centre, Room A4 21, 2075 Bayview Avenue, Toronto, ON, Canada M4N3M5 E-mail: sandra.black{at}sunnybrook.ca
Corticobasal syndrome (CBS) is a rare cognitive and movement disorder characterized by asymmetric rigidity, apraxia, alien-limb phenomenon, cortical sensory loss, myoclonus, focal dystonia, and dementia. It occurs along the clinical spectrum of frontotemporal lobar degeneration (FTLD), which has recently been shown to segregate with truncating mutations in progranulin (PGRN), a multifunctional growth factor thought to promote neuronal survival. This study identifies a novel splice donor site mutation in the PGRN gene (IVS7+1G
A) that segregates with CBS in a Canadian family of Chinese origin. We confirmed the absence of the mutant PGRN allele in the RT–PCR product which supports the model of haploinsufficiency for PGRN-linked disease. This report of mutation in the PGRN gene in CBS extends the evidence for genetic and phenotypic heterogeneity in FTLD spectrum disorders.
Key Words: Corticobasal syndrome; frontotemporal lobar degeneration; progranulin; gene; mutation
Abbreviations: CBS, corticobasal syndrome; CBD, corticobasal degeneration; CHMP2B, chromatin-modifying protein 2B; FTD, frontotemporal dementia; FTLD, frontotemporal lobar degeneration; MAPT, microtubule-associated protein tau; PGRN, progranulin; PPA, primary progressive aphasia; PSP, progressive supranuclear palsy; RT-PCR, reverse transcriptase-polymerase chain reaction
.
Received August 4, 2006. Revised August 31, 2006. Accepted September 1, 2006.
*These authors contributed equally to the work.
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