title: Study of deep intronic sequence exonization in a Japanese neonate with a mitochondrial trifunctional protein deficiency.
abstract: Mitochondrial trifunctional protein (MTP) comprises heterooctamer alpha4beta4 and a deficiency in this protein causes a mitochondrial long-chain beta-oxidation defect. Here, we describe the molecular basis of an MTPbeta-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.
authors.affiliation: Department of Pediatrics, Shimane University Faculty of Medicine, 89-1 Enya, Izumo, Shimane 693-8501, Japan. jamiyan@med.shimane-u.ac.jp
authors.forename: Jamiyan
authors.initials: J
authors.lastname: Purevsuren
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Fukao
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Seiji
authors.initials: S
authors.lastname: Fukuda
authors.forename: Hironori
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Seiji
authors.initials: S
authors.lastname: Yamaguchi
mesh_terms: D044466:Asian People / Q000235:genetics; D002478:Cells, Cultured; D018389:Codon, Nonsense; D005091:Exons; D017809:Fatal Outcome; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D007438:Introns; D008052:Lipid Metabolism, Inborn Errors / Q000201:enzymology / Q000235:genetics*; D063991:Mitochondrial Trifunctional Protein; D009097:Multienzyme Complexes / Q000172:deficiency / Q000235:genetics*; D016254:Mutagenesis, Insertional; D020125:Mutation, Missense; D022821:RNA Splice Sites
chemical_list: D018389:Codon, Nonsense; D009097:Multienzyme Complexes; D022821:RNA Splice Sites; D063991:Mitochondrial Trifunctional Protein