Considerable advancements in genomic medicine since the Human Genome Project have provided molecular diagnoses to many families with rare diseases, including rare pediatric neurological diseases (RPND). These advancements have paved the way for personalized medicine, substantially increasing our understanding of human physiology and biochemical pathways. They have also opened new avenues for innovative and more effective treatments, benefiting not only those with rare diseases but also individuals with more common conditions.
However, despite these advancements and the decreasing cost of high-throughput sequencing, many regions worldwide remain underrepresented in human genetic research. Even in developed countries with access to state-of-the-art medical facilities, many families remain without a definitive diagnosis. A major challenge in diagnosing neurogenetic disorders is the difficulty in interpreting sequence variants and the high prevalence of variants of uncertain significance, largely owing to the incomplete catalog of human variants across populations. This issue is further exacerbated by the scarcity of individuals with genetically confirmed rare diseases, driven by limited access to next-generation sequencing and comprehensive genetic testing for the majority of people globally.
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Acknowledgements
We are grateful for the important support from patients and families, our UK and international collaborators, brainbank and biobanks, and are grateful for essential funding from The Wellcome Trust, The Medical Research Council (MRC), The Chung Lab at Boston Children’s Hospital/Harvard Medical School, The Mutiple System Atrophy (MSA) Trust, The National Institute for Health Research University College London Hospitals Biomedical Research Centre (NIHR-BRC), The Michael J. Fox Foundation (MJFF), The Fidelity Trust, Rosetrees Trust, The Dolby Family fund, Alzheimer's Research UK (ARUK), MSA Coalition, The Guarantors of Brain, Cerebral Palsy Alliance, Friedreich’s Ataxia Research Alliance (FARA), European Academy of Neurology (EAN) and the National Institutes of Health (NIH) NeuroBioBank, Queen Square BrainBank, Queen Square Genomics and The MRC Brainbank Network. We want to thank A. Ussembayeva for her assistance in creating and designing the manuscript figure.
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Authors and Affiliations
Department of Neurology, South Kazakhstan Medical Academy, Shymkent, Kazakhstan
Rauan Kaiyrzhanov&Nazira Zharkinbekova
Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK
Rauan Kaiyrzhanov,Viorica Chelban,Jana Vandrovcova,Valentina Turchetti,Stephanie Efthymiou,Shahryar Alavi,Rahema Mohammad,John Hardy,Reza Maroofian&Henry Houlden
MediClub Hospital, Baku, Azerbaijan
Ulviyya Guliyeva&Sughra Guliyeva
Department of Neurology, Avicenna Tajik State Medical University, Dushanbe, Tajikistan
Manizha Ganieva&Maksudjon Isrofilov
Department of Neurology and Neurosurgery, National Institute of Health, Yerevan, Armenia
Zaruhi Tavadyan,Mariam Isayan&Samson G. Khachatryan
MediClub Georgia Medical Center, Tbilisi, Georgia
Tamar Gachechiladze,Nazi Tabatadze,Ekaterina Kurua&Gia Melikishvili
Fetal-Neonatal Neuroimaging & Developmental Science Center, Division of Newborn Medicine, Boston Children’s Hospital, Boston, MA, USA
Kamran Salayev
Department of Neurology, Tbilisi State Medical University, Tbilisi, Georgia
Mariam Kekenadze&Maia Beridze
Department of Neurology and Epilepsy, Arabkir Medical Complex, Yerevan, Armenia
Biayna Sukhudyan&Ani Gevorgyan
Department of Neurology, Yerevan State Medical University, Yerevan, Armenia
Artsruni Hakobyan
Neurology Department, Hb Guven Clinic, Baku, Azerbaijan
Rima Ibadova
Neuroscience Department, M.Iashvili Central Children’s Hospital, Tbilisi, Georgia
Teona Shatirishvili&Nana Nino Tatishvili
Faculty of Medicine, Khoja Akhmet Yassawi International Kazakh-Turkish University, Turkestan, Kazakhstan
Nigara Yerkhojayeva
Department of Neurology and Neurosurgery, Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan
Kairgali Koneev
Neurolab clinic, Almaty, Kazakhstan
Dauren Zhumakhanov&Askhat Mukushev
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
Askhat Mukushev
Department of Neurology, Astana Medical University, Astana, Kazakhstan
Altynshash Jaxybayeva
Department of Neurology of Early Age, National Research Center for Maternal and Child Health, Astana, Kazakhstan
Alissa Nauryzbayeva
Children Neurology Hospital, Baku, Azerbaijan
Saadat Badalova&Naila Zeyniyeva
Neurology Department, Azerbaijan Medical University, Baku, Azerbaijan
Ilaha Hajiyeva
Republican Pediatric Center, Baku, Azerbaijan
Leyla Alakbarov
Neuron Medical Center, Baku, Azerbaijan
Aynur Zeynalova
Neurobiology and Medical Genetics Laboratory, “Nicolae Testemitanu” State University of Medicine and Pharmacy, Chisinau, Republic of Moldova
Viorica Chelban
Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK
David Murphy
Department of Molecular and Medical Genetics, Tbilisi State Medical University, Tbilisi, Georgia
Tinatin Tkemaladze
Department of Paediatrics, Givi Zhvania Pediatric Academic Clinic, Tbilisi State Medical University, Tbilisi, Georgia
Tinatin Tkemaladze
Shashkin Clinic, Almaty, Kazakhstan
Chingiz Shashkin
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Contributions
R.K. and R. Maroofian wrote the paper. N. Zharkinbekova, U.G., M.G., Z.T., T.G., K.S., S.G., M. Isayan, M.K., B.S., A.G., A.H., R.I., N.T., E.K., T.S., N.Y., K.K., D.Z., A.M., A.J., A.N., M. Isrofilov, S.B., N. Zeyniyeva, I.H., L.A., A.Z., V.C., J.V., V.T., D.M., S.E., S.A., R. Mohammad, T.T., C.S., N.N.T., M.B., S.G.K., G.M., J.H. and H.H. reviewed the paper and provided feedback.
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Correspondence to Rauan Kaiyrzhanov.
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Nature Genetics thanks Salman Kirmani for their contribution to the peer review of this work.
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Kaiyrzhanov, R., Zharkinbekova, N., Guliyeva, U. et al. Elucidating the genomic basis of rare pediatric neurological diseases in Central Asia and Transcaucasia. Nat Genet (2024). https://doi.org/10.1038/s41588-024-02016-x
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DOI: https://doi.org/10.1038/s41588-024-02016-x
