TY - JOUR
T1 - Symmetrical corticobasal syndrome caused by a novel c.314dup progranulin mutation
AU - Dopper, Elise G.P.
AU - Seelaar, Harro
AU - Chiu, Wang Zheng
AU - De Koning, Inge
AU - Van Minkelen, Rick
AU - Baker, Matthew C.
AU - Rozemuller, Annemieke J.M.
AU - Rademakers, Rosa
AU - Van Swieten, John C.
N1 - Funding Information:
Funding This work was supported by Stichting Dioraphte grant 09-02-03-00 (to J.C.v.S.) and NIH grant R01 NS065782-01 (to R.R.).
PY - 2011/11
Y1 - 2011/11
N2 - 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.
AB - 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.
KW - Corticobasal syndrome (CBS)
KW - Frontotemporal lobar degeneration (FTLD)
KW - Progranulin (GRN)
KW - TDP-43
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U2 - 10.1007/s12031-011-9626-z
DO - 10.1007/s12031-011-9626-z
M3 - Article
C2 - 21863316
AN - SCOPUS:84860390154
SN - 0895-8696
VL - 45
SP - 354
EP - 358
JO - Journal of Molecular Neuroscience
JF - Journal of Molecular Neuroscience
IS - 3
ER -