Analysis of polyglutamine-coding repeats in the TATA-binding protein in different neurodegenerative diseases

Wu, Yih Ru; Fung, Hon Chung; Lee-Chen, Guey Jen; Gwinn‐Hardy, Katrina; Ro, Long Sun; Chen, S. T.; Hsieh-Li, Hsiu Mei; Lin, Hsueh-Yi; Cao, Lin; Li, S. N.; Chen, C. M.

doi:10.1007/s00702-004-0197-9

Cited by 27 publications

(20 citation statements)

References 30 publications

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“…The majority of the pedigrees have been identified in patients from Germany-Austria (approx 20 families) [2,16,31,[42][43][44][45], and from Japan (13 families) [19,27,28,38]. Additional SCA17 families were identified in Taiwan [23,41], USA [34], and Europe (Fig. 3) [8,12,17,24,36].…”

Section: Discussionmentioning

confidence: 95%

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: Discussionmentioning

confidence: 95%

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

et al. 2007

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“…This new genetic entity was subsequently identified in familial ADCA cases and was shown to differ in several aspects from other polyglutaminopathies (33)(34)(35). Pathological expansions were also found in patients with an HD-like phenotype (HDL4) or with clinical features compatible with Alzheimer, Parkinson's or Creutzfeldt-Jakob disease, highlighting the clinical heterogeneity of this genetic entity (36)(37)(38).…”

Section: Sca17/hdl4mentioning

confidence: 94%

“…This repeat is impure and is encoded by 3 CAG stretches, interrupted by 1 to 3 CAA codons ( Table I). The glutamine stretch is polymorphic in the normal population and large population studies (w5000 control chromosomes) have determined that the normal range is between 25 to 42 residues, most alleles containing 32 to 39 repeats (11,(33)(34)(35)37,40,(43)(44)(45). The allelic distribution varies slightly, however, according to the ethnic/geographical origins (43,45).…”

Section: Tata-box Binding Proteinmentioning

confidence: 98%

“…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%

“…Most families/cases are from Japan (n517 families) (11,34,38,50,67) and Germany (n519 families) (33,48,49,52,54,55,68), a distribution reminiscent of SCA6, which is also frequent in both these countries. The remaining families, when the origins have been mentioned, are as follows: nine from Italy (15,46,53,56,58,69), three from Taiwan (37,51), two from England (70), two from France (36), and one each from Belgium (35), the USA (57) and Portugal (47). The frequency of SCA17 ranges from 0.3 to 3% among studies of ADCA families (11,15,35,38,47,48,67) but represents less than 1% of HD-like patients (36,49).…”

Section: Epidemiology and Relative Frequency Of Sca17/ Hdl4mentioning

confidence: 99%

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

Stevanin

Brice

2008

Cerebellum

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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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Hereditary parkinsonism: Parkinson disease look‐alikes—An algorithm for clinicians to “PARK” genes and beyond

2009

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In the past decade, a number of genetic causes of parkinsonism have been identified. As a consequence, clinicians have to consider an increasing range of differential diagnoses when confronted with a patient with parkinsonism with a positive family history. While well-established monogenic forms with PARK acronyms have been reviewed extensively, less emphasis has been placed on other inherited conditions that may also present with signs of parkinsonism or even mimic idiopathic Parkinson's disease clinically. In this review, we focus on three different scenarios in patients with an overall early age of onset of parkinsonism: (i) atypical features in patients with mutations in one of the "PARK" genes; (ii) classical parkinsonism due to mutations in "other than-PARK" genes or yet other genes where parkinsonism may be a well-recognized, concomitant, or even an isolated feature; (iii) atypical parkinsonism in other genetic disorders which are, however, typically characterized by features other than parkinsonism. Atypical features in patients from Group I include, for example, a slower disease course (PARK2, PARK6, PARK7) or dementia (PARK1/4, PARK14). Conditions in Group II have been designated by a DYT or SCA acronym (for example, DYT5 or SCA3) and also include patients with heterozygous GBA mutations, mitochondrial gene mutations. Group III comprises mutations in the FMR1, MAPT, GRN, ATP7B, PANK2, FBXO7, CHAC, FTL1, Huntingtin, JPH3 genes, and a number of even rarer, miscellaneous conditions.

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Analysis of polyglutamine-coding repeats in the TATA-binding protein in different neurodegenerative diseases

Cited by 27 publications

References 30 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)

Hereditary parkinsonism: Parkinson disease look‐alikes—An algorithm for clinicians to “PARK” genes and beyond

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