A glimpse of the genetics of young-onset Parkinson’s disease in Central Asia
Kaiyrzhanov R. Aitkulova A. Vandrovcova J. Murphy D. Zharkinbekova N. Shashkin C. Akhmetzhanov V. Kaishibayeva G. Karimova A. Myrzayev Z. Murray M. Khaibullin T. Hardy J. Houlden H.
June 2021John Wiley and Sons Inc
Molecular Genetics and Genomic Medicine
2021#9Issue 6
Background: Knowledge of the genetic background of many human diseases is currently lacking from genetically undiscovered regions, including Central Asia. Kazakhstan is the first Central Asian country where the genetic studies of Parkinsons disease (PD) have been emerging since it had become a member of the International Parkinson Disease Genomics Consortium. Here we report on the results of whole-exome sequencing (WES) in 50 young-onset PD (YOPD) cases from Kazakhstan. Methodology: WES was performed on 50 unrelated individuals with YOPD from Kazakhstan. Exome data were screened for novel/ultra-rare deleterious variants in known and candidate PD genes. Copy number variants and small indels were also called. Results: Only three cases (6%) were found to be positive for known PD genes including two unrelated familial PD cases with LRRK2 p.(Arg1441Cys) and one case with a homozygous pathogenic PRKN p.(Arg84Trp) variant. Four cases had novel and ultra-rare variants of uncertain significance in LRRK2, DNAJC13, and VPS35. Novel deleterious variants were found in candidate Mendelian PD genes including CSMD1, TNR, EIF4G1, and ATP13A3. Eight cases harbored the East Asian-specific LRRK2 p.(Ala419Val) variant. Conclusions: The low diagnostic yield in our study might imply that a significant proportion of YOPD cases in Central Asia remains unresolved. Therefore, a better understanding of the genetic architecture of PD among populations of Central Asian ancestry and the pathogenicity of numerous rare variants should be further investigated. WES is a valuable technique for large-scale YOPD genetic studies in Central Asia.
age of onset , Central Asia , genetics , Kazakhstan , LRRK2 , Parkinsons disease , Parkinsons disease genetics , young-onset
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Department of Neuromuscular Disorders, Institute of Neurology, University College London, London, United Kingdom
Department of Molecular Genetics, National Center for Biotechnology, Nur-Sultan, Kazakhstan
Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London, United Kingdom
Department of Neurology, South Kazakhstan Medical Academy, Shymkent, Kazakhstan
Contemporary Neurology and Neurorehabilitation Clinic Shashkin Clinic, Almaty, Kazakhstan
Institute of Neurology and Neurorehabilitation Named After Smagul Kaishibayev, Almaty, Kazakhstan
Kazakh Medical University of Continuing Study, Almaty, Kazakhstan
Department of Neurology, Semey Medical University, Semey, Kazakhstan
Department of Neuromuscular Disorders
Department of Molecular Genetics
Department of Clinical and Movement Neurosciences
Department of Neurology
Contemporary Neurology and Neurorehabilitation Clinic Shashkin Clinic
Institute of Neurology and Neurorehabilitation Named After Smagul Kaishibayev
Kazakh Medical University of Continuing Study
Department of Neurology
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