Objective: To perform the genetic study of autosomal dominant spinocerebellar ataxia (ADSCA) cases from Kazakhstan.

Background: Spinocerebellar ataxias (SCAs) is a large group of hereditary cerebellar ataxias presenting with progressive gait imbalance, hand dysmetria, dysarthria, nystagmus, and additional neurological and non-neurological signs. Trinucleotide repeat expansion ataxias form the most common types of ADSCAs (1). The distribution of the different ADSCA types varies between ethnicities (2). Data on ADSCA genetics is lacking in Kazakhstan.

Method: Twenty three families with autosomal dominant family history of SCA from Kazakhstan were genetically studied at the Institute of Neurology University College London. Tethering polymerase chain reaction and Fragment analysis were used to identify the number of CAG repeats in ATXN1,2,3, and 7, CACNA1A,  PPP2R2B, and TBP genes. The study was approved by the local ethics of Shymkent Medical Academy, Kazakhstan (Protocol № 9/15.12.2015).

Results: The twenty-three ADSCA families had the following ethnic composition: 19 Kazakh families, two Russian, one Azerbaijani, and one Uzbek family all residing in Kazakhstan. Nine families were found to be positive for CAG expansions in ATXN1. The expansions were present in 21 cases (including 3 predictive testings) from those nine families. The mean age at disease onset (AAO) was 36.06±8.3 years old, and the mean disease duration (DD) was 8.6±5.6 years. The mean number of CAG expansions in ATXN1 was 48.9±4.4 (range 44-58). Two index cases from two families were found to be positive for SCA2 with the AAO of 26 and 36 years old, DD 5 and 10 years, and the number of CAG expansions of 42 and 38 respectively. One large family with 7 affected was positive for SCA7. The median AAO for this family was 46 years old (range 16-60), mean disease duration was 4,75±1.2, and the mean number of CAG expansions was 43.4 ± 4.9 (range 40-54). All the affected members of SCA7 family had a progressive visual impairment. The rest of the families (n=11) were negative for CAG expansions in trinucleotide repeat ADSCAs and were sent for exome sequencing. All of the positive families in our study were of Kazakh ethnicity.

Conclusion: The most common type of ADSCA in Kazakhstan is SCA1. Further genetic studies on larger ADSCA cohorts in Kazakhstan are required to identify the accurate frequency of the remaining types of CAG repeat ADSCAs.

References: 1. Bird TD. Hereditary ataxia overview. Gene reviews. 1998. https://www.ncbi.nlm.nih.gov/sites/books/NBK1138/ 2. Jayadev S, Bird TD. Hereditary ataxias: overview. Genet Med. 2013;15:673–83.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-genetic-study-of-autosomal-dominant-spinocerebellar-ataxia-in-kazakhstan/