Spinocerebellar ataxia type 17 associated with an expansion of 42 glutamine residues in TATA-box binding protein gene.
BACKGROUND
Spinocerebellar ataxia type 17 (SCA17) is caused by abnormal expansions of CAG/CAA trinucleotides within the TATA-box binding protein gene (TBP). The currently accepted critical threshold of abnormal expansions is ≥43.


OBJECTIVE
To investigate the minimal CAG/CAA expansion within the TBP in SCA17.


RESULTS
285 patients with autosomal-dominant ataxia were examined, and abnormal or borderline expansions of CAG/CAA within TBP in eight cases were found. Of those, four patients from three families had exactly 42 CAG/CAA trinucleotides, that is, one codon less than the currently accepted critical threshold of 43. The four patients presented with a relatively benign phenotype. All had dysdiadochokinesia and dysarthria. Mild gait ataxia was observed in three of the four patients.


CONCLUSIONS
The reference definition of at least 43 CAG/CAA codons for pathological SCA17 alleles should be lowered to 42.
Nolte
D
D
Institut für Humangenetik, Justus-Liebig Universität Giessen, Giessen, Germany. dagmar.nolte@humangenetik.med.uni-giessen.de
Sobanski
E
E
Wissen
A
A
Regula
J U
JU
Lichy
C
C
Müller
U
U
D000328:Adult; D000368:Aged; D000483:Alleles; D001284:Atrophy; D002531:Cerebellum / Q000473:pathology; D002869:Chromosome Aberrations; D003062:Codon; D005260:Female; D005799:Genes, Dominant / Q000235:genetics*; D005973:Glutamine / Q000235:genetics*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D019683:Penetrance; D020754:Spinocerebellar Ataxias / Q000175:diagnosis / Q000235:genetics*; D035181:TATA-Box Binding Protein / Q000235:genetics*; D019680:Trinucleotide Repeat Expansion; D055815:Young Adult
D003062:Codon; D035181:TATA-Box Binding Protein; D005973:Glutamine