Clinical relevance of zebrafish for gene variants testing. Proof-of-principle with SMN1/SMA.

ABSTRACT: SMA results from SMN1 gene-LOF, with disease severity linked to the level of remaining SMN protein. Revolutionary treatments exist but should be implemented before symptoms appear. Newborn screenings are increasingly used to identify patients requiring therapy. However, for novel mutations, clinicians lack robust tools to predict pathogenicity before irreversible damage occurs. To address this, we deployed a zebrafish model presenting smn1-LOF, exhibiting progressive motor defects and death by only six days of age. We evaluated two SMN1-variants (VUS) identified in newborns awaiting definite diagnosis and treatment recommendations. We demonstrated that while known pathogenic variants did not change the disease course, wild-type SMN1 and both patient variants rescued SMA hallmarks in zebraf

SUBMITTER: Brett, William Stringer 

PROVIDER: S-SCDT-10_1038-S44321-025-00355-8 | biostudies-other |

REPOSITORIES: biostudies-other