Novel

amyotrophic lateral sclerosis genetic association studies genetic marker genetic variant motor neuron disease stathmin-2 structural variation

Journal

Frontiers in aging neuroscience
ISSN: 1663-4365
Titre abrégé: Front Aging Neurosci
Pays: Switzerland
ID NLM: 101525824

Informations de publication

Date de publication:
2021
Historique:
received: 25 01 2021
accepted: 02 03 2021
entrez: 12 4 2021
pubmed: 13 4 2021
medline: 13 4 2021
Statut: epublish

Résumé

There is a critical need to establish genetic markers that explain the complex phenotypes and pathogenicity of ALS. This study identified a polymorphism in the Stathmin-2 gene and investigated its association with sporadic ALS (sALS) disease risk, age-of onset and survival duration. The candidate CA repeat was systematically analyzed using PCR, Sanger sequencing and high throughput capillary separation for genotyping. Stathmin-2 expression was investigated using RT-PCR in patient olfactory neurosphere-derived (ONS) cells and RNA sequencing in laser-captured spinal motor neurons. In a case-control analysis of a combined North American sALS cohort ( We report a novel non-coding CA repeat in Stathmin-2 which is associated with sALS disease risk and has disease modifying effects. The potential value of this variant as a disease marker and tool for cohort enrichment in clinical trials warrants further investigation.

Identifiants

DOI: 10.3389/fnagi.2021.658226 PMID: 33841129 PMC: PMC8033025
pubmed: 33841129
doi: 10.3389/fnagi.2021.658226
pmc: PMC8033025
doi:

Types de publication

Journal Article

Langues

eng

Pagination

658226

Informations de copyright

Copyright © 2021 Theunissen, Anderton, Mastaglia, Flynn, Winter, James, Bedlack, Hodgetts, Fletcher, Wilton, Laing, MacShane, Needham, Saunders, Mackay-Sim, Melamed, Ravits, Cleveland and Akkari.

Déclaration de conflit d'intérêts

FT, RA, LF, and PA hold the International patent application No. PCT/AU2020/051330 Discovery of informative structural variations within the STMN2 gene associated with sporadic Motor Neurone Disease. AS was employed by company Zinfandel Pharmaceuticals. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Auteurs

Frances Theunissen (F)

Perron Institute for Neurological and Translational Science, Nedlands, WA, Australia.
Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Perth, WA, Australia.

Ryan S Anderton (RS)

Perron Institute for Neurological and Translational Science, Nedlands, WA, Australia.
Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Nedlands, WA, Australia.
School of Health Sciences, Institute for Health Research, The University of Notre Dame Australia, Fremantle, WA, Australia.

Frank L Mastaglia (FL)

Perron Institute for Neurological and Translational Science, Nedlands, WA, Australia.
Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Nedlands, WA, Australia.

Loren L Flynn (LL)

Perron Institute for Neurological and Translational Science, Nedlands, WA, Australia.
Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Perth, WA, Australia.
Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Nedlands, WA, Australia.

Samantha J Winter (SJ)

Perron Institute for Neurological and Translational Science, Nedlands, WA, Australia.
School of Health Sciences, Institute for Health Research, The University of Notre Dame Australia, Fremantle, WA, Australia.

Ian James (I)

Institute for Immunology and Infectious Disease, Murdoch University, Perth, WA, Australia.

Richard Bedlack (R)

Department of Neurology, Duke University, Durham, NC, United States.

Stuart Hodgetts (S)

Perron Institute for Neurological and Translational Science, Nedlands, WA, Australia.
School of Human Sciences, University of Western Australia, Nedlands, WA, Australia.

Sue Fletcher (S)

Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Perth, WA, Australia.
Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Nedlands, WA, Australia.

Steve D Wilton (SD)

Perron Institute for Neurological and Translational Science, Nedlands, WA, Australia.
Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Perth, WA, Australia.
Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Nedlands, WA, Australia.

Nigel G Laing (NG)

Centre for Medical Research, Harry Perkins Institute of Medical Research, The University of Western Australia, Perth, WA, Australia.

Mandi MacShane (M)

Centre for Medical Research, Harry Perkins Institute of Medical Research, The University of Western Australia, Perth, WA, Australia.

Merrilee Needham (M)

Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Perth, WA, Australia.
Faculty of Medicine, The University of Notre Dame Australia, Fremantle, WA, Australia.
Department of Neurology, Fiona Stanley Hospital, Murdoch, WA, Australia.

Ann Saunders (A)

Zinfandel Pharmaceuticals, Chapel Hill, NC, United States.

Alan Mackay-Sim (A)

Perron Institute for Neurological and Translational Science, Nedlands, WA, Australia.
Griffith Institute for Drug Discovery, Griffith University, Nathan, QLD, Australia.

Ze'ev Melamed (Z)

Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA, United States.
Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, United States.

John Ravits (J)

Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.

Don W Cleveland (DW)

Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA, United States.
Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, United States.
Department of Neurosciences, University of California, San Diego, La Jolla, CA, United States.

P Anthony Akkari (PA)

Perron Institute for Neurological and Translational Science, Nedlands, WA, Australia.
Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Perth, WA, Australia.
Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Nedlands, WA, Australia.
Department of Neurology, Duke University, Durham, NC, United States.

Classifications MeSH