Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Symmetrical corticobasal syndrome caused by a novel C.314dup progranulin mutation. 2186 16

Corticobasal degeneration (CBD) is a progressive neurodegenerative disorder described by Rebeiz et al. It is characterized by progressive, asymmetric, cortical (eg, apraxia, alien limb phenomena, cortical sensory loss, and myoclonus), and extrapyramidal (eg, rigidity, bradykinesia, dystonia, and tremor) dysfunction. However, CBD has many clinical phenotypes, and the features used for predicting CBD have low sensitivity. Therefore, the term corticobasal syndrome (CBS) has been used to characterize such clinical features, whereas the term CBD is used to refer to the pathological disorder. The most frequent causes of CBS are CBD, followed by Alzheimer's disease, progressive supranuclear palsy, frontotemporal lobar degeneration with TDP-43 pathology (sporadic and familial), Pick's disease, Lewy body disease, frontotemporal lobar degeneration with fused in sarcoma-positive inclusions, Creutzfeldt-Jakob disease, and mutations in the microtubule-associated protein tau (MAPT) and progranulin (GRN) genes. The topography of neurodegeneration dictates the clinical syndrome not according to the underlying pathology. Researchers have attempted to develop fluid biomarkers or imaging analysis for diagnosing CBS. The aim of this review was to highlight recent advances in CBS diagnosis and discuss future directions.
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PMID:[Corticobasal syndrome: recent advances and future directions]. 2248 19

Corticobasal syndrome (CBS) is a clinical syndrome presenting with progressive asymmetric bradykinesia, rigidity, and dystonia accompanied by cortical signs, such as apraxia, alien limb phenomena, cortical sensory loss, myoclonus, and mirror movements. CBS is associated with different pathological conditions including FTLD-tau (corticobasal degeneration, CBD; progressive supranuclear palsy, PSP: and Pick disease), FTLD-TDP, Alzheimer disease, Creutzfeldt-Jakob disease, and Parkinson disease/dementia with Lewy bodies. Among these, the most common pathology is CBD. In patients with familial and sporadic FTLD, MAPT, GRN and C9orf72 mutations are the three main causes of the disease, even though the C9orf72 mutation is rare in Japan. Patients with MAPT mutations present with FTLD-tau, and patients with GRN and C9orf72 mutations exhibit FTLD-TDP. FTLD is also associated with VCP, CHMP2B, TARDBP and FUS mutations, but each of these account for <1% of familial FTLD cases. In sporadic cases, the H1c haplotype and the rare p.A152T variant of MAPT are known to be associated with FTLD-tau, and the common genetic variant (rs5848) in the 3'-UTR of GRN is associated with FTLD-TDP. A recent genome-wide association study identified TMEM106B as a potential risk-modifying factor for FTLD-TDP, and STX6, EIF2AK3 and MOBP, for PSP. Despite major advances in genetic studies in recent years, the majority of sporadic CBS cases are genetically unsolved. Further studies are needed to unveil the genetic background of CBS. In this review, we discuss the recent advances related to the genetics of CBS, particularly about the genetics of FTLD.
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PMID:[The genetics of corticobasal syndrome]. 2330 Jan

SCA 17 is a rare, autosomal dominant disorder caused by TBP gene CAG/CAA repeat expansion. Ataxia and dementia are common. The presence of frontal dysfunction at outset of the disease may mimic frontotemporal dementia (FTD). Parkinsonism, chorea, dystonia, and pyramidal signs may occur. We report an Irish family with autosomal dominant partially penetrant frontal dementia with cerebellar atrophy due to SCA17 and present detailed neuropsychological assessment for the first time. A 44-year-old doctor presented with 18-month history of behavioral problems. She slowed down, became apathetic, and unable to multitask. She became more irritable and short tempered, and her work performance deteriorated. Brain MRI showed cerebellar atrophy and cerebellar hypometabolism was noted on FDG-PET. A sister developed personality changes at age 45 with apathy, and had problems with memory and social skills; another sister at age 39 became dysarthric and unsteady. A brother at age 52 demonstrated emotional lability, and became dysarthric, unsteady, and slowed down. Their mother aged 73 had an abnormal antalgic gait due to arthritis; their father was jocular and disinhibited. MAPT testing detected an exon 9 c.726C>T variant in the proband. Subsequent testing in nine siblings and both parents failed to show co-segregation with disease. SCA17 testing revealed a TBP gene 43 repeat expansion that co-segregated in all affected siblings and in the mother whose gait problems were initially attributed to arthritis. In over 80% of cases of FTD with clear autosomal dominant inheritance, causative gene defects involve MAPT, GRN, or C9orf72 mutations. A minority involves VCP, FUS, and CHMP2B. As evident from our case, SCA17 testing should also be considered, especially if cerebellar atrophy if found on imaging. Segregation analysis is crucial. MAPT variant (c.726C>T exon 9) detected in the family was deemed a polymorphism.
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PMID:Autosomal Dominant Gene Negative Frontotemporal Dementia-Think of SCA17. 3061 27