CRISPR-mediated gene correction links the ATP7A M1311V mutations with amyotrophic lateral sclerosis pathogenesis in one individual.

Amino Acid Substitution Amyotrophic Lateral Sclerosis / diagnosis CRISPR-Cas Systems Clustered Regularly Interspaced Short Palindromic Repeats Copper-Transporting ATPases / genetics DNA Mutational Analysis Gene Editing Genetic Association Studies Genetic Predisposition to Disease Humans Induced Pluripotent Stem Cells / cytology Male Mutation Neurons / metabolism RNA, Guide, Kinetoplastida Whole Genome Sequencing

Journal

Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179

Informations de publication

Date de publication:
20 01 2020
Historique:
received: 01 04 2019
accepted: 17 12 2019
entrez: 22 1 2020
pubmed: 22 1 2020
medline: 11 5 2021
Statut: epublish

Résumé

Amyotrophic lateral sclerosis (ALS) is a severe disease causing motor neuron death, but a complete cure has not been developed and related genes have not been defined in more than 80% of cases. Here we compared whole genome sequencing results from a male ALS patient and his healthy parents to identify relevant variants, and chose one variant in the X-linked ATP7A gene, M1311V, as a strong disease-linked candidate after profound examination. Although this variant is not rare in the Ashkenazi Jewish population according to results in the genome aggregation database (gnomAD), CRISPR-mediated gene correction of this mutation in patient-derived and re-differentiated motor neurons drastically rescued neuronal activities and functions. These results suggest that the ATP7A M1311V mutation has a potential responsibility for ALS in this patient and might be a potential therapeutic target, revealed here by a personalized medicine strategy.

Identifiants

DOI: 10.1038/s42003-020-0755-1 PMID: 31959876 PMC: PMC6970999
pubmed: 31959876
doi: 10.1038/s42003-020-0755-1
pii: 10.1038/s42003-020-0755-1
pmc: PMC6970999
doi:

Substances chimiques

RNA, Guide 0
ATP7A protein, human EC 7.2.2.8
Copper-Transporting ATPases EC 7.2.2.8

Types de publication

Case Reports Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

33

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Auteurs

Yeomin Yun (Y)

Department of Neurosurgery, Spine & Spinal Cord Institute, College of Medicine, Yonsei University, Seoul, 03722, South Korea.
Brain Korea 21 PLUS Project for Medical Science, College of Medicine, Yonsei University, Seoul, 03722, South Korea.

Sung-Ah Hong (SA)

Department of Chemistry, Hanyang University, Seoul, 04763, South Korea.
Research Institute for Natural Sciences, Hanyang University, Seoul, 04763, South Korea.
ORCID: 0000-0002-3280-5677

Ka-Kyung Kim (KK)

Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, 03722, South Korea.

Daye Baek (D)

Department of Neurosurgery, Spine & Spinal Cord Institute, College of Medicine, Yonsei University, Seoul, 03722, South Korea.
Brain Korea 21 PLUS Project for Medical Science, College of Medicine, Yonsei University, Seoul, 03722, South Korea.

Dongsu Lee (D)

Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, South Korea.

Ashwini M Londhe (AM)

Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul, 130-650, South Korea.
Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology, Seoul, 02792, South Korea.

Minhyung Lee (M)

Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, South Korea.
Department of Functional Genomics, KRIBB School of Bioscience, Korea University of Science and Technology, Daejeon, 34113, South Korea.

Jihyeon Yu (J)

Department of Chemistry, Hanyang University, Seoul, 04763, South Korea.

Zachary T McEachin (ZT)

Laboratory of Translational Cell Biology, Emory University School of Medicine, Atlanta, GA, 30322, USA.
ORCID: 0000-0002-2369-8726

Gary J Bassell (GJ)

Laboratory of Translational Cell Biology, Emory University School of Medicine, Atlanta, GA, 30322, USA.
Department of Cell Biology, Emory University, Atlanta, GA, 30322, USA.

Robert Bowser (R)

Department of Neurobiology, Barrow Neurological Institute and St. Joseph's Hospital and Medical Center, Phoenix, AZ, 85013, USA.

Chadwick M Hales (CM)

Department of Neurology, Emory University, Atlanta, GA, 30322, USA.

Sung-Rae Cho (SR)

Brain Korea 21 PLUS Project for Medical Science, College of Medicine, Yonsei University, Seoul, 03722, South Korea.
Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, 03722, South Korea.

Janghwan Kim (J)

Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, South Korea.
Department of Functional Genomics, KRIBB School of Bioscience, Korea University of Science and Technology, Daejeon, 34113, South Korea.

Ae Nim Pae (AN)

Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul, 130-650, South Korea.
Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology, Seoul, 02792, South Korea.

Eunji Cheong (E)

Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, South Korea.

Sangwoo Kim (S)

Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, 03722, South Korea.
ORCID: 0000-0001-5356-0827

Nicholas M Boulis (NM)

Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA, 30322, USA.

Sangsu Bae (S)

Department of Chemistry, Hanyang University, Seoul, 04763, South Korea. sangsubae@hanyang.ac.kr.
Research Institute for Natural Sciences, Hanyang University, Seoul, 04763, South Korea. sangsubae@hanyang.ac.kr.
ORCID: 0000-0003-3615-8566

Yoon Ha (Y)

Department of Neurosurgery, Spine & Spinal Cord Institute, College of Medicine, Yonsei University, Seoul, 03722, South Korea. HAYOON@yuhs.ac.
Brain Korea 21 PLUS Project for Medical Science, College of Medicine, Yonsei University, Seoul, 03722, South Korea. HAYOON@yuhs.ac.

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questionsmedicales.fr › Phénomènes génétiques › Mutagenèse › Substitution d'acide aminé › CRISPR-mediated gene correction links the...
questionsmedicales.fr › Maladies métaboliques et nutritionnelles › Maladies métaboliques › Troubles de l'homéostasie des protéines › Protéinopathies TDP-43 › Sclérose latérale amyotrophique › CRISPR-mediated gene correction links the...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Épigenèse génétique › Extinction de l'expression des gènes › Systèmes CRISPR-Cas › CRISPR-mediated gene correction links the...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Séquences répétées en tandem › Clustered regularly interspaced short palindromic repeats › CRISPR-mediated gene correction links the...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › P-type ATPases › Copper-transporting ATPases › CRISPR-mediated gene correction links the...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Analyse de séquence d'ADN › Analyse de mutations d'ADN › CRISPR-mediated gene correction links the...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Génie génétique › Édition de gène › CRISPR-mediated gene correction links the...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Études d'associations génétiques › CRISPR-mediated gene correction links the...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Prédisposition génétique à une maladie › CRISPR-mediated gene correction links the...
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questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN non traduit › Petit ARN non traduit › ARN guide › CRISPR-mediated gene correction links the...
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