CRISPR-mediated gene correction links the ATP7A M1311V mutations with amyotrophic lateral sclerosis pathogenesis in one individual.
Commun Biol
; 3(1): 33, 2020 01 20.
Article
en En
| MEDLINE
| ID: mdl-31959876
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Sustitución de Aminoácidos
/
Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas
/
Edición Génica
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ATPasas Transportadoras de Cobre
/
Esclerosis Amiotrófica Lateral
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Mutación
Tipo de estudio:
Diagnostic_studies
/
Etiology_studies
/
Prognostic_studies
Límite:
Humans
/
Male
Idioma:
En
Revista:
Commun Biol
Año:
2020
Tipo del documento:
Article
País de afiliación:
Corea del Sur