Dementia, ataxia, extrapyramidal features, and epilepsy: phenotype spectrum in two Italian families with spinocerebellar ataxia type 17

Michele, G. De; Maltecca, Francesca; Carella, Massimo; Volpe, G.; Orio, Marcello; Falco, Antonietta de; Gombia, S.; Servadio, Antonio; Casari, Giorgio; Filla, Alessandro; Bruni, Amalia C.

doi:10.1007/s10072-003-0112-4

Cited by 53 publications

(37 citation statements)

References 6 publications

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“…In the present study we screened a more heterogeneous group of patients including patients with different clinical presentation, either ataxic or Huntington-like, and patients with or without a positive family history for hereditary movement disorders. Our novel results, combined with those of other Italian reports [9,25], indicate that a total of 14 SCA17 families have been identified so far in Italy. In our referral-based sample, SCA17 represents the third most frequent SCA genotype, after SCA1 and SCA2 (Fig.…”

Section: Discussionsupporting

confidence: 48%

Spinocerebellar ataxia type 17 (SCA17): Oculomotor phenotype and clinical characterization of 15 Italian patients

et al. 2007

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SCA17 is a rare type of autosomal dominant spinocerebellar ataxia caused by a CAG/CAA expansion in the gene encoding the TATA-binding protein (TBP). We screened for triplet expansion in the TBP gene 110 subjects with progressive cerebellar ataxia and 94 subjects with Huntington-like phenotype negative at specific molecular tests. SCA17 mutation-positive subjects were found in both groups of patients. Expanded alleles with > or = 44 CAG/CAA repeats were identified in 11 individuals and in 4 non-symptomatic relatives. Eleven de novo diagnosed patients and four patients previously reported underwent extensive clinical, neuroradiological and oculographic examination. Cerebellar signs and symptoms were present in all cases; 80% of the patients had mild to severe cognitive deficits; 66% of patients showed choreic movements; pyramidal signs, bradykinesia and dystonia were observed in approx 50% of the cases. MRI demonstrated cortical and cerebellar atrophy in all patients, whereas neurophysiological examination excluded signs of peripheral nervous system involvement. Oculographic examinations were performed in 9 out of 15 patients and showed a distinct pattern of oculomotor abnormalities, characterized by impairment of smooth pursuit, defects in the saccade accuracy, normal saccade velocity, hyperreflexia of vestibuloocular reflexes, and absence of nystagmus. In summary, this study presents one of the largest series of SCA17 patients in Europe. In our group of patients, SCA17 represents the third most frequent SCA genotype. Our clinical data confirm the large variability in SCA17 phenotypic presentation, and indicate that a peculiar combination of neuroradiological, electrophysiological and oculomotor findings is recognizable in SCA17.

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Section: Discussionsupporting

confidence: 48%

Spinocerebellar ataxia type 17 (SCA17): Oculomotor phenotype and clinical characterization of 15 Italian patients

et al. 2007

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“…The threshold for pathological expansions varies according to the study from 43 to 45 repeats (36,38,(46)(47)(48). Sporadic patients carrying from 43 to 63 repeats have been identified, while affected members of families with dominant transmission of the disease carry between 45 and 66 CAG/CAA repeats (34)(35)(36)(37)(38)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57).…”

Section: Tata-box Binding Proteinmentioning

confidence: 99%

Spinocerebellar ataxia 17 (SCA17) and Huntington’s disease-like 4 (HDL4)

2008

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Spinocerebellar ataxia 17 (SCA17) or Huntington's disease-like-4 is a neurodegenerative disease caused by the expansion above 44 units of a CAG/CAA repeat in the coding region of the TATA box binding protein (TBP) gene leading to an abnormal expansion of a polyglutamine stretch in the corresponding protein. Alleles with 43 and 44 repeats have been identified in sporadic cases and their pathogenicity remains uncertain. Furthermore, incomplete penetrance of pathological alleles with up to 49 repeats has been suggested. The imperfect nature of the repeat makes intergenerational instability extremely rare and de novo mutations are most likely the result of partial duplications. This is one of the rarer forms of autosomal dominant cerebellar ataxia but the associated phenotype is often severe, involving various systems (cerebral cortex, striatum, and cerebellum), with extremely variable age at onset (range: 3-75 years) and clinical presentation. This gene is thought to account for a small proportion of patients with a Huntington's disease-like phenotype and cerebellar signs. Parkinson's disease-like, Creutzfeldt-Jakob disease-like and Alzheimer disease-like phenotypes have also been described with small SCA17 expansions. The abnormal protein is expressed at the same level as its normal counterpart and forms neuronal intranuclear inclusions containing other proteins involved in protein folding or degradation. The increase in the size of the glutamine stretch enhances transcription in vitro, probably leading to transcription deregulation. Interestingly, the TBP protein mutated in SCA17 is recruited in the inclusions of other polyglutaminopathies, suggesting its involvement in the transcription down-regulation observed in these diseases.

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“…SCA 17 is a rare form of autosomal dominant neurodegenerative disease caused by an expansion of a CAG triplet repeat in the TBP gene (located in chromosome 6q27) which encodes for the TATA binding protein, a transcription initiation factor 3,4,[51][52][53] .…”

Section: Sca 17mentioning

confidence: 99%

Spinocerebellar ataxias

Teive¹

2009

Arq. Neuro-Psiquiatr.

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-Spinocerebellar ataxias (SCAs) constitute a heterogeneous group of neurodegenerative diseases characterized by progressive cerebellar ataxia in association with some or all of the following conditions: ophthalmoplegia, pyramidal signs, movement disorders, pigmentary retinopathy, peripheral neuropathy, cognitive dysfunction and dementia. Objective: To carry out a clinical and genetic review of the main types of SCA. Method: The review was based on a search of the PUBMED and OMIM databases. Results: Thirty types of SCAs are currently known, and 16 genes associated with the disease have been identified. The most common types are SCA type 3, or Machado-Joseph disease, SCA type 10 and SCA types 7, 2, 1 and 6. SCAs are genotypically and phenotypically very heterogeneous. A clinical algorithm can be used to distinguish between the different types of SCAs. Conclusions: Detailed clinical neurological examination of SCA patients can be of great help when assessing them, and the information thus gained can be used in an algorithm to screen patients before molecular tests to investigate the correct etiology of the disease are requested.KEY WORDS: spinocerebellar ataxias, cerebellar atrophy, genotype, phenotype. Ataxias espinocerebelaresResumo -As ataxias espinocerebelares (AECs) compreendem um grupo heterogeneo de enfermidades neurodegenerativas, que se caracterizam pela presença de ataxia cerebelar progressiva, associada de forma variada com oftalmoplegia, sinais piramidais, distúrbios do movimento, retinopatia pigmentar, neuropatia periférica, disfunção cognitiva e demência. Objetivo: Realizar uma revisão clínico-genética dos principais tipos de AECs. Método: A revisão foi realizada através da pesquisa pelo sistema do PUBMED e do OMIM. Resultados: Na atualidade existem cerca de 30 tipos de AECs, com a descoberta de 16 genes. Os tipos mais comuns são a AEC tipo 3, ou doença de Machado-Joseph, a AEC tipo 10, e as AECs tipo 7, 2 1, e 6. As AECs apresentam grande heterogeneidade genotípica e fenotípica. Pode-se utilizar um algoritmo clínico para a pesquisa dos diferentes tipos de AECs. Conclusões: O exame clínico neurológico minucioso nos pacientes com AECs pode auxiliar sobremaneira na avaliação clínica destes pacientes, utilizando-se desta forma de um algoritmo, com os dados clínicos, que pode servir como um instrumento de triagem para a solicitação dos testes de genética molecular, para a correta investigação etiológica.

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Dementia, ataxia, extrapyramidal features, and epilepsy: phenotype spectrum in two Italian families with spinocerebellar ataxia type 17

Cited by 53 publications

References 6 publications

Spinocerebellar ataxia type 17 (SCA17): Oculomotor phenotype and clinical characterization of 15 Italian patients

Spinocerebellar ataxia type 17 (SCA17): Oculomotor phenotype and clinical characterization of 15 Italian patients

Spinocerebellar ataxia 17 (SCA17) and Huntington’s disease-like 4 (HDL4)

Spinocerebellar ataxias

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