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Increased Diagnostic Yield of Spastic Paraplegia with or Without Cerebellar Ataxia Through Whole-Genome Sequencing.
Kim, Aryun; Kumar, Kishore R; Davis, Ryan L; Mallawaarachchi, Amali C; Gayevskiy, Velimir; Minoche, Andre E; Walls, Zachary; Kim, Han-Joon; Jang, Mihee; Cowley, Mark J; Choi, Ji-Hyun; Shin, Chaewon; Sue, Carolyn M; Jeon, Beomseok.
Afiliação
  • Kim A; Department of Neurology, Chungbuk National University Hospital, Cheongju-si, South Korea.
  • Kumar KR; Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia. kkum4618@uni.sydney.edu.au.
  • Davis RL; Department of Neurogenetics, Kolling Institute, University of Sydney Faculty of Medicine and Health Northern Clinical School and Royal North Shore Hospital, St Leonards, NSW, Australia. kkum4618@uni.sydney.edu.au.
  • Mallawaarachchi AC; Department of Neurology, Royal North Shore Hospital, Northern Sydney Local Health District, St Leonards, NSW, Australia. kkum4618@uni.sydney.edu.au.
  • Gayevskiy V; Molecular Medicine Laboratory, Concord Hospital, Sydney, NSW, Australia. kkum4618@uni.sydney.edu.au.
  • Minoche AE; Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
  • Walls Z; Department of Neurogenetics, Kolling Institute, University of Sydney Faculty of Medicine and Health Northern Clinical School and Royal North Shore Hospital, St Leonards, NSW, Australia.
  • Kim HJ; Division of Genomics and Epigenetics, Garvan Institute of Medical Research, Sydney, NSW, Australia.
  • Jang M; Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
  • Cowley MJ; Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
  • Choi JH; Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
  • Shin C; Faculty of Engineering & Information Technologies, The University of Sydney, Sydney, NSW, Australia.
  • Sue CM; Department of Neurology, Movement Disorder Center, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
  • Jeon B; Department of Neurology, Presbyterian Medical Center, Jeonju, South Korea.
Cerebellum ; 18(4): 781-790, 2019 Aug.
Article em En | MEDLINE | ID: mdl-31104286
Inherited disorders of spasticity or ataxia exist on a spectrum with overlapping causative genes and phenotypes. We investigated the use of whole-genome sequencing (WGS) to detect a genetic cause when considering this spectrum of disorders as a single group. We recruited 18 Korean individuals with spastic paraplegia with or without cerebellar ataxia in whom common causes of hereditary cerebellar ataxia and hereditary spastic paraplegia had been excluded. We performed WGS with analysis for single nucleotide variants, small insertions and deletions, copy number variants (CNVs), structural variants (SVs) and intronic variants. Disease-relevant variants were identified in ABCD1 (n = 3), CAPN1 (n = 2), NIPA1 (n = 1) and PLA2G6 (n = 1) for 7/18 patients (38.9%). A 'reverse phenotyping' approach was used to clarify the diagnosis in individuals with PLA2G6 and ABCD1 variants. One of the ABCD1 disease-relevant variants was detected on analysis for intronic variants. No CNV or SV causes were found. The two males with ABCD1 variants were initiated on monitoring for adrenal dysfunction. This is one of only a few studies to analyse spastic-ataxias as a continuous spectrum using a single approach. The outcome was improved diagnosis of unresolved cases for which common genetic causes had been excluded. This includes the detection of ABCD1 variants which had management implications. Therefore, WGS may be particularly relevant to diagnosing spastic ataxias given the large number of genes associated with this condition and the relatively high diagnostic yield.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Paraplegia / Ataxia Cerebelar Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Adolescent / Adult / Aged / Child / Female / Humans / Male / Middle aged Idioma: En Revista: Cerebellum Assunto da revista: CEREBRO Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Coréia do Sul

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Paraplegia / Ataxia Cerebelar Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Adolescent / Adult / Aged / Child / Female / Humans / Male / Middle aged Idioma: En Revista: Cerebellum Assunto da revista: CEREBRO Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Coréia do Sul