Objective: To analyze the genetic background of hereditary chorea in Kazakhstani population.

Background: Hereditary chorea (HC) is a group of inherited movement disorders presenting with chorea, hyper- and hypo-kinetic movement disorders, and other neurological and non-neurological symptoms (1). Although, Huntington’s disease (HD) is far the most common cause of HC in the word, dentatorubropallidoluisian atrophy and HD-like 2 are not infrequent causes of HC in Japan and sub-Saharan Africa respectively (2). The genetic causes and prevalence of HC in Kazakhstan is unknown.

Method: 45 patients and their 38 first degree clinically unaffected relatives from 26 unrelated families with an autosomal dominant history of chorea were consecutively recruited from two movement disorders centers in Kazakhstan. Genetic testing was performed at the Institute of Neurology University College London. Fragment analysis was conducted in all the affected and unaffected cases to identify the number of CAG repeats in HTT gene. HD negative cases were planned to be tested for other causes of HC. The study was approved by the local ethics of Shymkent Medical Academy, Kazakhstan (Protocol № 9/15.12.2015).

Results: The clinical diagnoses for the 45 patients with CH were consistent with probable HD. There was one case of juvenile HD (onset at 8 years old) presenting with severe parkinsonism and cognitive decline. The mean age at the HD motor signs onset in the cohort, excluding the juvenile case, was 38.6±4.7 years old, the mean disease duration was 8.3±4.3 years. The ethnic composition of the cohort were made of 15 Kazakh, 9 Russian, and 2 Uzbek families. Fragment analysis revealed fully penetrant CAG expansions in HTT gene in all the patients and their 17 clinically unaffected relatives. The mean number of the expanded CAG repeats was 44.85±3.7, range 40-66. The mean length of the CAG tract (MLCAGT) in the normal alleles of HD patients and the chromosomes of all negative cases was 19.4±2.7. This is more than MLCAGT in Europeans (18.4) (3) and might imply that the prevalence of HD in Kazakhstan is approximately 4-5 for 100 000 population.

Conclusion: HD is the common and only cause of HC in our Kazakhstani cohort. The length of the CAG tract in our cohort could suggest that the prevalence of HD in Kazakhstan is closer to Western rather that East Asian HD prevalence figures. Further studies are required in Kazakhstan to investigate HTT haplogroups.

References: 1. Edwards, S. (2016). Parkinson’s disease and other movement disorders. Oxford University Press. 2nd edition. 2. Schneider, S.A., and Bird, T. (2016). Huntington’s Disease, Huntington’s Disease Look‐Alikes‎, and Benign Hereditary Chorea: What’s New? Movement disorder clinical practice. doi:10.1002/mdc3.12312 3. Squitieri et al. (1994). DNA haplotype analysis of Huntington disease reveals clues to the origins and mechanisms of CAG expansion and reasons for geographic variations of prevalence. Human Molecular Genetics, 1994, Vol. 3, No. 12 2103-2114

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-genetic-study-of-hereditary-chorea-in-kazakhstan/