title: Symmetrical corticobasal syndrome caused by a novel C.314dup progranulin mutation.
abstract: Corticobasal syndrome (CBS) is characterised by asymmetrical parkinsonism and cognitive impairment. The underlying pathology varies between corticobasal degeneration, progressive supranuclear palsy, Alzheimer's disease, Creutzfeldt-Jakob disease and frontotemporal lobar degeneration sometimes in association with GRN mutations. A 61-year-old male underwent neurological examination, neuropsychological assessment, MRI, and HMPAO-SPECT at our medical centre. After his death at the age of 63, brain autopsy, genetic screening and mRNA expression analysis were performed. The patient presented with slow progressive walking disabilities, non-fluent language problems, behavioural changes and forgetfulness. His family history was negative. He had primitive reflexes, rigidity of his arms and postural instability. Later in the disease course he developed dystonia of his left leg, pathological crying, mutism and dysphagia. Neuropsychological assessment revealed prominent ideomotor and ideational apraxia, executive dysfunction, non-fluent aphasia and memory deficits. Neuroimaging showed symmetrical predominant frontoparietal atrophy and hypoperfusion. Frontotemporal lobar degeneration (FTLD)-TDP type 3 pathology was found at autopsy. GRN sequencing revealed a novel frameshift mutation c.314dup, p.Cys105fs and GRN mRNA levels showed a 50% decrease. We found a novel GRN mutation in a patient with an atypical (CBS) presentation with symmetric neuroimaging findings. GRN mutations are an important cause of CBS associated with FTLD-TDP type 3 pathology, sometimes in sporadic cases. Screening for GRN mutations should also be considered in CBS patients without a positive family history.
authors.affiliation: Department of Neurology, Erasmus Medical Center, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands.
authors.forename: Elise G P
authors.initials: EG
authors.lastname: Dopper
authors.forename: Harro
authors.initials: H
authors.lastname: Seelaar
authors.forename: Wang Zheng
authors.initials: WZ
authors.lastname: Chiu
authors.forename: Inge
authors.initials: I
authors.lastname: de Koning
authors.forename: Rick
authors.initials: R
authors.lastname: van Minkelen
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Baker
authors.forename: Annemieke J M
authors.initials: AJ
authors.lastname: Rozemuller
authors.forename: Rosa
authors.initials: R
authors.lastname: Rademakers
authors.forename: John C
authors.initials: JC
authors.lastname: van Swieten
mesh_terms: D001344:Autopsy; D001480:Basal Ganglia Diseases / Q000473:pathology* / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology; D017809:Fatal Outcome; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000473:pathology* / Q000503:physiopathology*; D000077153:Progranulins; D013577:Syndrome
chemical_list: C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins