A glimpse of the genetics of young‐onset Parkinson’s disease in Central Asia

Molecular Genetics & Genomic Medicine

Zhanybek Myrzayev¹  Chingiz Shashkin¹  David Murphy²  Akbota Aitkulova³  Talgat Khaibullin⁴  Nazira Zharkinbekova⁵  Vadim Akhmetzhanov⁵  Jana Vandrovcova⁶  Rauan Kaiyrzhanov⁶  Henry Houlden⁶  Malgorzata Murray⁶  John Hardy⁶  Gulnaz Kaishibayeva⁷  Altynay Karimova⁸ 

[1] Contemporary Neurology and Neurorehabilitation Clinic "Shashkin Clinic" Almaty Kazakhstan;Department of Clinical and Movement Neurosciences UCL Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery London UK;Department of Molecular GeneticsNational Center for Biotechnology Nur‐Sultan Kazakhstan;Department of Neurology Semey Medical University Semey Kazakhstan;Department of Neurology South Kazakhstan Medical Academy Shymkent Kazakhstan;Department of Neuromuscular Disorders Institute of Neurology University College London London UK;Institute of Neurology and Neurorehabilitation Named After Smagul Kaishibayev Almaty Kazakhstan;Kazakh Medical University of Continuing Study Almaty Kazakhstan;

关键词: age of onset;    Central Asia;    genetics;    Kazakhstan;    LRRK2;    Parkinson's disease;   

DOI  :  10.1002/mgg3.1671

来源: DOAJ

【 摘 要 】

ABSTRACT 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 Parkinson's 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.

【 授权许可】

Unknown