An Update on the Adult-Onset Hereditary Cerebellar Ataxias: Novel Genetic Causes and New Diagnostic Approaches.

Autor: Rudaks LI; Molecular Medicine Laboratory and Neurology Department, Concord Repatriation General Hospital, Sydney, Australia. laura.rudaks@gmail.com.; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia. laura.rudaks@gmail.com.; Genomics and Inherited Disease Program, The Garvan Institute of Medical Research, Sydney, Australia. laura.rudaks@gmail.com.; Clinical Genetics Unit, Royal North Shore Hospital, Sydney, Australia. laura.rudaks@gmail.com., Yeow D; Molecular Medicine Laboratory and Neurology Department, Concord Repatriation General Hospital, Sydney, Australia.; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.; Genomics and Inherited Disease Program, The Garvan Institute of Medical Research, Sydney, Australia.; Neurodegenerative Service, Prince of Wales Hospital, Sydney, Australia.; Neuroscience Research Australia, Sydney, Australia., Ng K; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.; Neurology Department, Royal North Shore Hospital, Sydney, Australia., Deveson IW; Genomics and Inherited Disease Program, The Garvan Institute of Medical Research, Sydney, Australia.; Faculty of Medicine, University of New South Wales, Sydney, Australia., Kennerson ML; Molecular Medicine Laboratory and Neurology Department, Concord Repatriation General Hospital, Sydney, Australia.; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.; The Northcott Neuroscience Laboratory, ANZAC Research Institute, Sydney Local Health District, Sydney, Australia., Kumar KR; Molecular Medicine Laboratory and Neurology Department, Concord Repatriation General Hospital, Sydney, Australia.; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.; Genomics and Inherited Disease Program, The Garvan Institute of Medical Research, Sydney, Australia.; Faculty of Medicine, University of New South Wales, Sydney, Australia.; Faculty of Medicine, St Vincent's Healthcare Campus, UNSW Sydney, Sydney, Australia.
Jazyk: angličtina
Zdroj: Cerebellum (London, England) [Cerebellum] 2024 Oct; Vol. 23 (5), pp. 2152-2168. Date of Electronic Publication: 2024 May 18.
DOI: 10.1007/s12311-024-01703-z
Abstrakt: The hereditary cerebellar ataxias (HCAs) are rare, progressive neurologic disorders caused by variants in many different genes. Inheritance may follow autosomal dominant, autosomal recessive, X-linked or mitochondrial patterns. The list of genes associated with adult-onset cerebellar ataxia is continuously growing, with several new genes discovered in the last few years. This includes short-tandem repeat (STR) expansions in RFC1, causing cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS), FGF14-GAA causing spinocerebellar ataxia type 27B (SCA27B), and THAP11. In addition, the genetic basis for SCA4, has recently been identified as a STR expansion in ZFHX3. Given the large and growing number of genes, and different gene variant types, the approach to diagnostic testing for adult-onset HCA can be complex. Testing methods include targeted evaluation of STR expansions (e.g. SCAs, Friedreich ataxia, fragile X-associated tremor/ataxia syndrome, dentatorubral-pallidoluysian atrophy), next generation sequencing for conventional variants, which may include targeted gene panels, whole exome, or whole genome sequencing, followed by various potential additional tests. This review proposes a diagnostic approach for clinical testing, highlights the challenges with current testing technologies, and discusses future advances which may overcome these limitations. Implementing long-read sequencing has the potential to transform the diagnostic approach in HCA, with the overall aim to improve the diagnostic yield.
(© 2024. The Author(s).)
Databáze: MEDLINE
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