title: Characterization of point mutations in the same arginine codon in three unrelated patients with ornithine transcarbamylase deficiency.
abstract: Point mutations in the X-linked ornithine transcarbamylase (OTC) gene have been detected at the same Taq I restriction site in 3 of 24 unrelated probands with OTC deficiency. A de novo mutation could be traced in all three families to an individual in a prior generation, confirming independent recurrence. The DNA sequence in the region of the altered Taq I site was determined in the three probands. In two unrelated male probands with neonatal onset of severe OTC deficiency, a guanine (G) to adenine (A) mutation on the sense strand (antisense cytosine [C] to thymine [T]) was found, resulting in glutamine for arginine at amino acid 109 of the mature polypeptide. In the third case, where the proband was a symptomatic female, C to T (sense strand) transition converted residue 109 to a premature stop. These results support the observation that Taq I restriction sites, which contain an internal CG, are particularly susceptible to C to T transition mutation due to deamination of a methylated C in either the sense or antisense strand. The OTC gene seems especially sensitive to C to T transition mutation at arginine codon 109 because either a nonsense mutation or an extremely deleterious missense mutation will result.
authors.affiliation: Howard Hughes Medical Institute, Philadelphia, PA 19104.
authors.forename: A
authors.initials: A
authors.lastname: Maddalena
authors.forename: J E
authors.initials: JE
authors.lastname: Spence
authors.forename: W E
authors.initials: WE
authors.lastname: O'Brien
authors.forename: R L
authors.initials: RL
authors.lastname: Nussbaum
mesh_terms: D000328:Adult; D001120:Arginine / Q000235:genetics*; D001483:Base Sequence; D015139:Blotting, Southern; D002675:Child, Preschool; D003001:Cloning, Molecular; D003062:Codon / Q000302:isolation & purification*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D015345:Oligonucleotide Probes; D009954:Ornithine Carbamoyltransferase / Q000235:genetics / Q000302:isolation & purification; D020163:Ornithine Carbamoyltransferase Deficiency Disease; D010375:Pedigree; D012333:RNA, Messenger / Q000302:isolation & purification*
chemical_list: D003062:Codon; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D001120:Arginine; D009954:Ornithine Carbamoyltransferase