Screening for proteins with polyglutamine expansions in autosomal dominant cerebellar ataxias.

1. Hum Mol Genet. 1996 Dec;5(12):1887-92.

Screening for proteins with polyglutamine expansions in autosomal dominant
cerebellar ataxias.

Stevanin G(1), Trottier Y, Cancel G, Dürr A, David G, Didierjean O, Bürk K,
Imbert G, Saudou F, Abada-Bendib M, Gourfinkel-An I, Benomar A, Abbas N,
Klockgether T, Grid D, Agid Y, Mandel JL, Brice A.

Author information:
(1)INSERM U289, Hôpital de la Salpêtrière, Paris, France.

Expansion of trinucleotide CAG repeats coding for polyglutamine has been
implicated in five neurodegenerative disorders, including spinocerebellar ataxia
(SCA) 1 and SCA3 or Machado-Joseph disease (SCA3/MJD), two forms of type I
autosomal dominant cerebellar ataxias (ADCA). Using the 1C2 antibody which
specifically recognizes large polyglutamine tracts, particularly those that are
expanded, we recently reported the detection of proteins with pathological
glutamine expansions in lymphoblasts from another form of ADCA type I, SCA2, as
well as from patients presenting with the distinct phenotype of ADCA type II. We
now have screened a large series of patients with ADCA or isolated cases with
cerebellar ataxia, for the presence of proteins with polyglutamine expansions. A
150 kDa SCA2 protein was detected in 16 out of 40 families with ADCA type I. This
corresponds to 24% of all ADCA type I families, which is much more frequent than
SCA1 in this series of patients (13%). The signal intensity of the SCA2 protein
was negatively correlated to age at onset, as expected for an expanded and
unstable trinucleotide repeat mutation. The disease segregated with markers
closely linked to the SCA2 locus in all identified SCA2 families. In addition, a
specific 130 kDa protein, which segregated with the disease, was detected in
lymphoblasts of patients from nine families with ADCA type II. It was also
visualized in the cerebral cortex of one of the patients, demonstrating its
translation in the nervous system. Finally, no new disease-related proteins
containing expanded polyglutamine tracts could be detected in lymphoblasts from
the remaining patients with ADCA or isolated cases with cerebellar ataxia.

DOI: 10.1093/hmg/5.12.1887
PMID: 8968739 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus