Genetic analysis of GLT8D1 and ARPP21 in Australian familial and sporadic amyotrophic lateral sclerosis

Sandrine Chan Moi Fat; Emily P McCann; Kelly L Williams; Lyndal Henden; Natalie A Twine; Denis C Bauer; Roger Pamphlett; Matthew C Kiernan; Dominic B Rowe; Garth A Nicholson; Jennifer A Fifita; Ian P Blair

doi:10.1016/j.neurobiolaging.2021.01.005

Genetic analysis of GLT8D1 and ARPP21 in Australian familial and sporadic amyotrophic lateral sclerosis

Neurobiol Aging. 2021 May:101:297.e9-297.e11. doi: 10.1016/j.neurobiolaging.2021.01.005. Epub 2021 Jan 16.

Affiliations

¹ Macquarie University Centre for Motor Neuron Disease Research, Department of Biomedical Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, New South Wales, Australia.
² Macquarie University Centre for Motor Neuron Disease Research, Department of Biomedical Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, New South Wales, Australia; Australian eHealth Centre, Commonwealth Scientific and Industrial Research Organization, Health & Biosecurity Flagship, Sydney, New South Wales, Australia.
³ Australian eHealth Centre, Commonwealth Scientific and Industrial Research Organization, Health & Biosecurity Flagship, Sydney, New South Wales, Australia; Department of Biomedical Sciences, Faculty of Medicine Health and Human Sciences, Macquarie University, Sydney, New South Wales, Australia; Applied BioSciences, Faculty of Science and Engineering, Macquarie University, Sydney, New South Wales, Australia.
⁴ Discipline of Pathology, University of Sydney, Sydney, New South Wales, Australia; Department of Neuropathology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia; Brain and Mind Centre, University of Sydney, Sydney, New South Wales, Australia.
⁵ Brain and Mind Centre, University of Sydney, Sydney, New South Wales, Australia; Institute of Clinical Neurosciences, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
⁶ Macquarie University Centre for Motor Neuron Disease Research, Department of Biomedical Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, New South Wales, Australia; Department of Clinical Medicine, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, New South Wales, Australia.
⁷ Macquarie University Centre for Motor Neuron Disease Research, Department of Biomedical Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, New South Wales, Australia; Northcott Neuroscience Laboratory, ANZAC Research Institute, Sydney, New South Wales, Australia; Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia; Molecular Medicine Laboratory, Concord Hospital, Sydney, New South Wales, Australia.
⁸ Macquarie University Centre for Motor Neuron Disease Research, Department of Biomedical Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, New South Wales, Australia. Electronic address: jennifer.fifita@mq.edu.au.

PMID: 33581934
DOI: 10.1016/j.neurobiolaging.2021.01.005

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease caused by the progressive degeneration of motor neurons. Recently, genetic variants in GLT8D1 and ARPP21 were associated with ALS in a cohort of European descent. A synergistic relationship was proposed between ALS associated variants in GLT8D1 and ARPP21. We aimed to determine the prevalence of genetic variation in GLT8D1 and ARPP21 in an Australian cohort of familial (n = 81) and sporadic ALS (n = 618) cases using whole-exome and whole-genome sequencing data. No novel mutations were identified in either gene, nor was there significant enrichment of protein-altering sequence variation among ALS cases. GLT8D1 and ARPP21 mutations are not a common cause of ALS in Australian familial and sporadic cohorts.

Keywords: Amyotrophic lateral sclerosis; GLT8D1 and ARPP21; Gene screening; Whole-genome sequencing.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amyotrophic Lateral Sclerosis / genetics*
Australia
Cohort Studies
Exome Sequencing
Female
Genetic Variation / genetics*
Genome-Wide Association Study / methods*
Glycosyltransferases / genetics*
Humans
Male
Negative Results*
Phosphoproteins / genetics*
White People / genetics
Whole Genome Sequencing

Substances

Phosphoproteins
cyclic AMP-regulated phosphoprotein ARPP-21
GLT8D1 protein, human
Glycosyltransferases