title: Four novel gene mutations in five Japanese male patients with neonatal or late onset OTC deficiency: application of PCR-single-strand conformation polymorphisms for all exons and adjacent introns [corrected].
abstract: Ornithine transcarbamylase deficiency (OTC), the most common inborn error of the urea cycle, shows an X-linked inheritance with frequent new mutations. Southern blots reveal only a small percent of the mutation, but amplification of cDNA or genomic DNA using the polymerase chain reaction (PCR) followed by DNA sequencing, has contributed greatly to overcoming this difficulty. Problems remaining are the limited availability of fresh liver samples for preparation of intact mRNA in the former case, and there are primer sequences for PCR for only some exons in the latter case. Here, we report the structures of intron sequences which are long enough to analyze all exons and adjacent introns of the OTC gene using PCR and PCR single-strand conformation polymorphisms (PCR-SSCP). We carried out a DNA analysis of findings in five Japanese male patients with neonatal or late onset form. Five patients had mutations in the protein coding region. C to G (S192R), A to T (D196V), A to G (T264A), T to C (M268T), and C to T (R277W) substitutions. The first four of these were novel missense mutations and the presence of the mutation was confirmed in the corresponding families.
authors.affiliation: Department of Pediatrics, Kumamoto University, School of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Matsuura
authors.forename: R
authors.initials: R
authors.lastname: Hoshide
authors.forename: C
authors.initials: C
authors.lastname: Setoyama
authors.forename: K
authors.initials: K
authors.lastname: Shimada
authors.forename: Y
authors.initials: Y
authors.lastname: Hase
authors.forename: T
authors.initials: T
authors.lastname: Yanagawa
authors.forename: M
authors.initials: M
authors.lastname: Kajita
authors.forename: I
authors.initials: I
authors.lastname: Matsuda
mesh_terms: D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D003001:Cloning, Molecular; D004247:DNA; D004252:DNA Mutational Analysis; D004277:DNA, Single-Stranded / Q000737:chemistry; D005091:Exons; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007438:Introns; D007564:Japan; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009690:Nucleic Acid Conformation; D009954:Ornithine Carbamoyltransferase / Q000235:genetics; D020163:Ornithine Carbamoyltransferase Deficiency Disease; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic
chemical_list: D004277:DNA, Single-Stranded; D004247:DNA; D009954:Ornithine Carbamoyltransferase