Study of deep intronic sequence exonization in a Japanese neonate with a mitochondrial trifunctional protein deficiency

Mitochondrial trifunctional protein (MTP) comprises heterooctamer α4β4 and a deficiency in this protein causes a mitochondrial long-chain β-oxidation defect. Here, we describe the molecular basis of an MTPβ-subunit deficiency in a Japanese neonate. Mutation screening at the genomic level including all exons and exon–intron boundaries identified a novel c.1136A > G (H346R) mutation in exon 13 of the maternal allele, but none in the paternal allele. Analysis by RT-PCR identified paternal-specific 106- and 56-bp intronic insertions between exons 7 and 8, which introduced premature terminations. This intronic exonization was caused by a deep intronic mutation in intron 7 on the paternal allele that generates a cryptic splice donor site. This is the first report of a deep intronic mutation in MTP deficiency.