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High Degree of Genetic Heterogeneity for Hereditary Cerebellar Ataxias in Australia.
Kang, Ce; Liang, Christina; Ahmad, Kate E; Gu, Yufan; Siow, Sue-Faye; Colebatch, James G; Whyte, Scott; Ng, Karl; Cremer, Philip D; Corbett, Alastair J; Davis, Ryan L; Roscioli, Tony; Cowley, Mark J; Park, Jin-Sung; Sue, Carolyn M; Kumar, Kishore R.
Affiliation
  • Kang C; Faculty of Medicine and Health, Kolling Institute of Medical Research, University of Sydney Northern Clinical School, St Leonards, Australia.
  • Liang C; Department of Neurogenetics, Kolling Institute, University of Sydney and Northern Sydney Local Health District, St Leonards, Australia.
  • Ahmad KE; Department of Neurology, Royal North Shore Hospital, St Leonards, Australia.
  • Gu Y; Department of Neurogenetics, Kolling Institute, University of Sydney and Northern Sydney Local Health District, St Leonards, Australia.
  • Siow SF; Department of Neurology, Royal North Shore Hospital, St Leonards, Australia.
  • Colebatch JG; Department of Neurogenetics, Kolling Institute, University of Sydney and Northern Sydney Local Health District, St Leonards, Australia.
  • Whyte S; Department of Neurology, Royal North Shore Hospital, St Leonards, Australia.
  • Ng K; Department of Neurogenetics, Kolling Institute, University of Sydney and Northern Sydney Local Health District, St Leonards, Australia.
  • Cremer PD; Department of Neurology, Royal North Shore Hospital, St Leonards, Australia.
  • Corbett AJ; Prince of Wales Clinical School and Neuroscience Research Australia, University of New South Wales, Randwick, Australia.
  • Davis RL; Institute of Neurological Sciences, Prince of Wales Hospital, Randwick, Australia.
  • Roscioli T; Department of Neurology, Gosford Hospital, Gosford, Australia.
  • Cowley MJ; Department of Neurology, Royal North Shore Hospital, St Leonards, Australia.
  • Park JS; Department of Neurology, Royal North Shore Hospital, St Leonards, Australia.
  • Sue CM; Department of Neurology, Concord Repatriation General Hospital, Concord, Australia.
  • Kumar KR; Faculty of Medicine and Health, Kolling Institute of Medical Research, University of Sydney Northern Clinical School, St Leonards, Australia.
Cerebellum ; 18(1): 137-146, 2019 Feb.
Article in En | MEDLINE | ID: mdl-30078120
Genetic testing strategies such as next-generation sequencing (NGS) panels and whole genome sequencing (WGS) can be applied to the hereditary cerebellar ataxias (HCAs), but their exact role in the diagnostic pathway is unclear. We aim to determine the yield from genetic testing strategies and the genetic and phenotypic spectrum of HCA in Australia by analysing real-world data. We performed a retrospective review on 87 HCA cases referred to the Neurogenetics Clinic at the Royal North Shore Hospital, Sydney, Australia. Probands underwent triplet repeat expansion testing; those that tested negative had NGS-targeted panels and WGS testing when available. In our sample, 58.6% were male (51/87), with an average age at onset of 37.1 years. Individuals with sequencing variants had a prolonged duration of illness compared to those with a triplet repeat expansion. The detection rate in probands for routine repeat expansion panels was 13.8% (11/80). NGS-targeted panels yielded a further 11 individuals (11/32, 34.4%), with WGS yielding 1 more diagnosis (1/3, 33.3%). NGS panels and WGS improved the overall diagnostic rate to 28.8% (23/80) in 14 known HCA loci. The genetic findings included novel variants in ANO10, CACNA1A, PRKCG and SPG7. Our findings highlight the genetic heterogeneity of HCAs and support the use of NGS approaches for individuals who were negative on repeat expansion testing. In comparison to repeat disorders, individuals with sequencing variants may have a prolonged duration of illness, consistent with slower progression of disease.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Cerebellar Ataxia / Genetic Heterogeneity Type of study: Observational_studies / Risk_factors_studies Limits: Adolescent / Adult / Aged / Child / Child, preschool / Female / Humans / Male / Middle aged Country/Region as subject: Oceania Language: En Journal: Cerebellum Journal subject: CEREBRO Year: 2019 Document type: Article Affiliation country: Australia Country of publication: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Cerebellar Ataxia / Genetic Heterogeneity Type of study: Observational_studies / Risk_factors_studies Limits: Adolescent / Adult / Aged / Child / Child, preschool / Female / Humans / Male / Middle aged Country/Region as subject: Oceania Language: En Journal: Cerebellum Journal subject: CEREBRO Year: 2019 Document type: Article Affiliation country: Australia Country of publication: United States