Objective: To report the detection of the first case of spinocerebellar ataxia 17 in Russian population.

Background: Autosomal dominant spinocerebellar ataxias (AD SCAs) are clinically and genetically heterogeneous progressive neurodegenerative disorders caused by mutations in about 40 different genetic loci. SCA 17 (aka Huntington’s disease-like 4 is a typical "polyglutamine disease" caused by the pathologic expansion of trinucleotide CAG/CAA repeats above 43 units in the TATA-box binding protein gene (TBP, locus 6q27). Clinical features of SCA 17 include trunk and limb ataxia, generalized chorea and dystonia, pyramidal signs, cognitive decline, epileptic seizures, psychiatric symptoms, etc. The prevalence of SCA 17 is unknown but very rare. About 100 families with SCA17 have been reported to date, and most of them are from Japan. No cases of SCA 17 were found in Russia until now.

Methods: Direct mutation screening was performed in a large Russian cohort of AD (n=42) and sporadic (n=110) SCA and Huntington’s disease-like unrelated cases with unidentified genetic defects. Molecular genetic study was conducted by fragment analysis, and the configuration of GAG/CAA repeat tracts was confirmed by direct sequencing in some cases. The subjects were clinically evaluated using standard neurological examination and neuropsychological testing. MRI and electroencephalography (EEG) were also performed routinely.

Results: Abnormal CAG/CAA repeat length (45 trinucleotide repeats) in exon 3 of TBP gene was found in young man aged 25. There was no family history of any neurologic disorders in this case. Clinical symptoms were presented since the age of 20 with steadily progressing trunk and limb ataxia, dysarthria, writing abnormalities. There were some rare episodes of losses of consciousness without convulsions in his medical history. No any other movement disorders were found during clinical examination, cognitive status was normal. MRI demonstrated symmetric moderate atrophy of cerebellar vermis and hemispheres; EEG revealed epileptic patterns in some regions of the brain.

Conclusions: Thus we observe “sporadic“ case of SCA 17 with incomplete clinical phenotype possibly due to reduced penetrance of the mutant gene. DNA study of proband’s parents are planned for the near future. So, we have reported the first observation of SCA 17 clinical case in Russian population.

« Back to 2016 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/spinocerebellar-ataxia-17-first-observation-in-russia/