Yun, Yeomin Hong, Sung-Ah Kim, Ka-Kyung Baek, Daye Lee, Dongsu ASHWINI MACHHINDRA LONDHE Lee, Minhyung Yu, Jihyeon McEachin, Zachary T. Bassell, Gary J. Bowser, Robert Hales, Chadwick M. Cho, Sung-Rae Kim, Janghwan Pae, Ae Nim Cheong, Eunji Kim, Sangwoo Boulis, Nicholas M. Bae, Sangsu Ha, Yoon 2024-01-19T18:31:05Z 2024-01-19T18:31:05Z 2022-01-25 2020-01 2399-3642 https://pubs.kist.re.kr/handle/201004/119114 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. Yeomin Yun, Sung-Ah Hong et al. compare the whole-genome sequence from a male with amyotrophic lateral sclerosis (ALS) to his healthy parents, identifying the M1311V variant in the X-lined ATP7A gene. They show that CRISPR-mediated gene correction in patient-derived neurons rescues neuronal activity. English Nature Publishing Group CRISPR-mediated gene correction links the ATP7A M1311V mutations with amyotrophic lateral sclerosis pathogenesis in one individual Article 10.1038/s42003-020-0755-1 1 Communications Biology, v.3, no.1 Communications Biology 3 1 Y scie scopus 000511413100002 2-s2.0-85078284707 Biology Multidisciplinary Sciences Life Sciences & Biomedicine - Other Topics Science & Technology - Other Topics Article P-TYPE ATPASES ALS NEURODEGENERATION ASSOCIATION MECHANISMS PHENOTYPE VARIANTS GENOMICS TOOL