Case Report: A novel deep intronic MFSD8 splice-altering variant causes CLN7 disease through pseudoexon inclusion.

A novel deep intronic MFSD8 variant, NM_001371596.2:c.999-556C>G, in a CLN7 patient is linked to aberrant 98-nt pseudoexon inclusion that disrupts normal splicing.

• Why it matters: Deep intronic pathogenic variants are often missed by exon-focused sequencing, leaving rare inherited disorders molecularly unsolved without functional confirmation.
• What they did: Trio whole-genome sequencing found a homozygous MFSD8 variant absent from population databases, and SpliceAI predicted cryptic splice activation; patient fibroblast RNA showed pseudoexon inclusion in 84% of MFSD8 transcripts, with a minigene assay reproducing the defect.
• The result: The pseudoexon inclusion caused a frameshift and premature termination codon, expanding the MFSD8 mutational spectrum and supporting molecular diagnosis by combining whole-genome sequencing with transcript analysis.

AI summary of the abstract · may contain errors · not medical advice · read the paper.