title: Identification of two new aberrant splicings in the ornithine carbamoyltransferase (OCT) gene in two patients with early and late onset OCT deficiency.
abstract: Ornithine carbamoyltransferase (OCT) is a liver-specific enzyme located in the mitochondrial matrix. OCT deficiency is an X-linked disease with a heterogeneous phenotype, even in affected males. We studied two male patients (K.M., K.G.) with early and late onset, respectively. OCT activity was zero in the autopsied liver of patient K.M. and was 6% of control in the biopsied liver of K.G. Sequencing of OCT cDNAs revealed exon 5 skipping in K.M., resulting from a T-to-C transition of the initial dinucleotide of the 5' splicing donor site of intron 5, and a G-to-T transversion at position +45 in exon 9 (L304F) in K.G., providing three OCT mRNAs of different lengths: a normally spliced transcript, 23 bp insertion of intron 8 and the first 50bp missing within exon 9. Exon 5 skipping and two other aberrant splicings produced stop codons early downstream in mature OCT mRNAs. Expression study of a missense allele, L304F, transfected to cultured Cos 1 cells revealed a 34.4% value of the control. The difference of OCT activities between the patient liver and transfected cells (6% vs. 34%) can be explained by this splicing abnormality.
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics*; D001483:Base Sequence; D015153:Blotting, Western; D002675:Child, Preschool; D018076:DNA, Complementary / Q000032:analysis / Q000096:biosynthesis; D006801:Humans; D007231:Infant, Newborn; D007438:Introns; D008099:Liver / Q000201:enzymology; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009954:Ornithine Carbamoyltransferase / Q000235:genetics*; D020163:Ornithine Carbamoyltransferase Deficiency Disease; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis
chemical_list: D018076:DNA, Complementary; D012333:RNA, Messenger; D009954:Ornithine Carbamoyltransferase