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

1. Cerebellum. 2008;7(2):170-8. doi: 10.1007/s12311-008-0016-1.

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

Stevanin G(1), Brice A.

Author information:
(1)INSERM U679, Groupe Pitié-Salpetrière, 47 Boulevard de l’Hopital, 75651 Paris
Cedex 13, France.

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.

DOI: 10.1007/s12311-008-0016-1
PMID: 18418687 [Indexed for MEDLINE]

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