SCA17 caused by homozygous repeat expansion in TBP due to partial isodisomy 6.
Eur J Hum Genet
; 11(8): 629-32, 2003 Aug.
Article
em En
| MEDLINE
| ID: mdl-12891385
ABSTRACT
An expanded polyglutamine domain in the TATA-binding protein (TBP) has been described in patients with spinocerebellar ataxia type 17 (SCA17) characterized by cerebellar ataxia associated with dementia. TBP is a general transcription initiation factor that regulates the expression of most eukaryotic genes transcribed by RNA polymerase II. SCA17, as an autosomal dominantly inherited progressive neurodegenerative disorder, is caused by heterozygous expansion of a CAG repeat coding for glutamine. Alleles with 27 to a maximum of 44 glutamine residues were found as the normal range, whereas expansions above 45 repeat units were considered pathological. Here, we present a patient with a very severe phenotype with a late onset but rapidly progressing ataxia associated with dementia and homozygous 47 glutamine residues caused by an apparent partial isodisomy 6. This extraordinary case has important implications for the insights of TBP and SCA17. The expanded polyglutamine domain in both TBP copies is not correlated with embryonic death indicating that the normal function of the protein is not disrupted by this kind of mutation but may account for the dementia seen in this patient.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cromossomos Humanos Par 6
/
Aberrações Cromossômicas
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Expansão das Repetições de Trinucleotídeos
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Ataxias Espinocerebelares
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Fatores Associados à Proteína de Ligação a TATA
Limite:
Adult
/
Female
/
Humans
Idioma:
En
Revista:
Eur J Hum Genet
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
Alemanha