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

ABSTRACT: Spinal muscular atrophy (SMA) results from SMN1 gene loss-of-function (LOF), with disease severity directly linked to the level of remaining SMN protein. Nusinersen, risdiplam, and onasemnogene abeparvovec are revolutionary treatments but should ideally be implemented before clinical symptoms appear. Because of this, prenatal and newborn screenings are increasingly used to identify common SMN1 variants and patients requiring therapy. However, for novel variants, clinicians lack robust analytic tools to predict pathogenicity before irreversible damage occurs. To address this gap, 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 of uncertain significance (VUS) identified in newborn infant

SUBMITTER: Stringer BW 

PROVIDER: S-EPMC12808650 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature