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)

Spinocerebellar ataxia type 17 (SCA17) is a dominant progressive neurodegenerative disorder, caused by a triplet repeat expansion within the TATA-binding protein. As well as ataxia and dementia, Parkinsonism and dystonia are common in SCA17. In some pedigrees focal dystonia in the absence of ataxia has been described as a main clinical feature. To evaluate the relevance of SCA17 mutations for primary dystonia, we examined the TBP repeat expansion in a series of 288 patients with different subtypes of primary torsion dystonia. We did not find any repeat sizes in the pathogenic range. We conclude that the SCA17 repeat expansion is not a common cause of familial and sporadic dystonia.
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PMID:Mutation at the SCA17 locus is not a common cause of primary dystonia. 1550 3

Introduction. Spinocerebellar ataxia 17 (SCA 17) is a rare autosomal dominant cerebellar ataxia (ADCA) caused by a CAG/CAA expansion in the TBP gene, reported from a limited number of countries. It is a very heterogeneous ADCA characterized by ataxia, cognitive decline, psychiatric symptoms, and involuntary movements, with some patients presenting with Huntington disease (HD) phenocopies. The SCA 17 expansion is stable during parent-child transmission and intrafamilial phenotypic homogeneity has been reported. However, significant phenotypic variability within families has also been observed. Report of the Family. We presently report a Greek family with a pathological expansion of 54 repeats at the SCA 17 locus that displayed remarkable phenotypic variability. Among 3 affected members, one presented with HD phenocopy; one with progressive ataxia, dementia, chorea, dystonia, and seizures, and one with mild slowly progressive ataxia with minor cognitive and affective symptoms. Conclusions. This is the first family with SCA 17 identified in Greece and highlights the multiple faces of this rare disorder, even within the same family.
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PMID:From mild ataxia to huntington disease phenocopy: the multiple faces of spinocerebellar ataxia 17. 2534 49

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