Spinocerebellar ataxia type 11 (SCA11) is an uncommon cause of dominant ataxia among French and German kindreds.

P. Bauer, G. Stevanin, C. Beetz, M. Synofzik, T. Schmitz-Hubsch, U. Wullner, E. Berthier, E. Ollagnon-Roman, O. Riess, S. Forlani, E. Mundwiller, A. Durr, L. Schols, A. Brice
Journal of Neurology, Neurosurgery & Psychiatry. 2010-07-28; 81(11): 1229-1232
DOI: 10.1136/jnnp.2009.202150

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1. J Neurol Neurosurg Psychiatry. 2010 Nov;81(11):1229-32. doi:
10.1136/jnnp.2009.202150. Epub 2010 Jul 28.

Spinocerebellar ataxia type 11 (SCA11) is an uncommon cause of dominant ataxia
among French and German kindreds.

Bauer P(1), Stevanin G, Beetz C, Synofzik M, Schmitz-Hübsch T, Wüllner U,
Berthier E, Ollagnon-Roman E, Riess O, Forlani S, Mundwiller E, Durr A, Schöls L,
Brice A.

Author information:
(1)Department of Medical Genetics, University of Tübingen, Tübingen, Germany.

BACKGROUND: At least 28 loci have been linked to autosomal dominant
spinocerebellar ataxia (ADCA). Causative genes have been cloned for 10 nucleotide
repeat expansions (SCA1, 2, 3, 6, 7, 8, 10, 12, 17 and 31) and six genes with
classical mutations (SCA5, 13, 14, 15/16, 27 and 28). Recently, a large British
pedigree linked to SCA11 has been reported to carry a mutation in the TTBK2 gene.
In order to assess the prevalence and phenotypic spectrum of SCA11, the authors
screened 148 index patients of predominantly German (n=69) and French (n=79)
descent with ADCA tested negative for a panel of SCA mutations (SCA1, 2, 3, 6, 7
and 17), for mutations in TTBK2.
METHODS: In the German ADCA cohort, the complete coding sequence of the TTBK2
gene was PCR-amplified and screened for mutations by high-resolution-melting
(HRM) analysis. In the French cohort, exons known to carry mutations were
directly sequenced. For both cohorts, the gene-dosage alterations were assessed
using a customised multiplex ligation probe amplification (MLPA) assay.
RESULTS: In two of 148 ADCA families–one German and one French–the authors
identified a potentially disease-causing SCA11 mutation. Interestingly, both
carried an identical two-basepair deletion (c.1306_1307delGA, p.D435fs448X in
exon 12) leading to a premature stop codon. Gene-dosage alterations were not
detected in the TTBK2 gene. Clinically, the SCA11 patients had phenotypic
characteristics as described before presenting with slowly progressive almost
pure cerebellar ataxia with normal life expectancy.
CONCLUSION: SCA11 presented as ADCA III according to Harding’s classification and
is a rare cause of spinocerebellar ataxia in Caucasians accounting for less than
1% of dominant ataxias in central Europe.

DOI: 10.1136/jnnp.2009.202150
PMID: 20667868 [Indexed for MEDLINE]

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