A Novel SLC26A4 Frameshift Variant Is Associated with Reduced Mutant-Allele RNA Abundance in Blood Leukocytes
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A novel SLC26A4 mutation, c.997_998insA, was identified in a 4-year-old child presenting with classic enlarged vestibular aqueduct (EVA). This single-nucleotide insertion causes a frameshift and introduces a premature termination codon (PTC), suggesting a potential role for nonsense-mediated mRNA decay (NMD). Although AlphaGenome predicted no appreciable reduction in RNA abundance, pyrosequencing demonstrated a significant decrease in the transcript level of the mutant allele compared with the wild-type allele in peripheral blood from the proband’s mother. These results indicate that the pathogenic mechanism of this SLC26A4 variant may arise primarily at the post-transcriptional (RNA regulation) level, rather than solely through altered protein function.
