Intronic PAH gene mutations cause a splicing defect by a novel mechanism involving U1snRNP binding downstream of the 5' splice site.
PLoS Genet 2018 Apr 23;14(4):e1007360. Epub 2018 Apr 23.
Centro de Biología Molecular Severo Ochoa UAM-CSIC, CEDEM, CIBERER, IdiPaz, Universidad Autónoma, Madrid, Spain.
Phenylketonuria (PKU), one of the most common inherited diseases of amino acid metabolism, is caused by mutations in the phenylalanine hydroxylase (PAH) gene. Recently, PAH exon 11 was identified as a vulnerable exon due to a weak 3' splice site, with different exonic mutations affecting exon 11 splicing through disruption of exonic splicing regulatory elements. In this study, we report a novel intron 11 regulatory element, which is involved in exon 11 splicing, as revealed by the investigated pathogenic effect of variants c. Read More