Ataxin-7 aggregation and ubiquitination in infantile SCA7 with 180 CAG repeats.
Extremely long (>150) CAG repeats are often used to create models of polyglutamine diseases yet are very rare in humans where they manifest as pediatric multisystem syndromes of little specificity. Here, we describe an infant with 180 CAG repeats in the spinocerebellar ataxia type 7 gene and focus on systemic ataxin-7 aggregation. This was found in many organs, including the cardiovascular system. In the brain, the hippocampus emerged as a principal site of ataxin-7 aggregation without cell loss. We note differential ubiquitination of aggregates and discuss how this may relate to selective vulnerability.
Ansorge
Olaf
O
Division of Neuropathology, Institute of Neurology, Queen Square, London, United Kingdom. olaf.ansorge@clneuro.ox.ac.uk
Giunti
Paola
P
Michalik
Andrej
A
Van Broeckhoven
Christine
C
Harding
Brian
B
Wood
Nicholas
N
Scaravilli
Francesco
F
D000067719:Ataxin-7; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010375:Pedigree; D020754:Spinocerebellar Ataxias / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D018911:Trinucleotide Repeats / Q000235:genetics*; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism*
C000593829:ATXN7 protein, human; D000067719:Ataxin-7; D009419:Nerve Tissue Proteins; D025801:Ubiquitin