Abstract
We describe six new mutations in the ornithine transcarbamylase (OTC) gene found in patients with OTC deficiency. These mutations were detected by single-strand conformational polymorphism analysis of amplified genomic DNA and characterized by direct sequencing of double-stranded DNA. Three of the mutations were found in males who had neonatal onset of hyperammonemia. The mutations are a single base deletion (guanine) in exon 5 at nucleotide 403 causing a frame-shift error, a guanine to adenine substitution at the 3′ end of intron 2 nucleotide 217 (-1) causing an acceptor splicing site error, and a guanine to adenine substitution at base 236 changing the code from glycine to glutamic acid at position 47 of the mature enzyme. Two different mutations were found in two males whose onset of clinical problems occurred after the neonatal period. One patient had a guanine to cytosine trans version in the sense strand of exon 3 at nucleotide 281 resulting in a substitution of threonine for arginine in position 62 of the mature OTC protein. This substitution changes the composition of the putative active site for carbamyl phosphate from Ser-Thr-Arg-Thr-Arg to Ser-Thr-Arg-Thr-Thr. The second patient has a guanine to thymine substitution at nucleotide 912 of the sense strand of exon 9, changing the code for leucine to phenylalanine in position 272 of the mature OTC protein. This changes a conserved domain of the gene likely to be the ornithine binding site from Phe-Leu-His-Cys-Leu-Pro to Phe-Leu-His-Cys-Phe-Pro. One female with OTC deficiency had a thymine to guanine substitution at nucleotide 1033, changing the code from tyrosine to aspartic acid at position 313 of the mature enzyme. We also confirmed an apparently common polymorphism in exon 8. An adenine or guanine in base 809 determines the code for a glutamine or an arginine, respectively, in position 238 of the mature OTC protein.
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Tuchman, M., Holzknecht, R., Gueron, A. et al. Six New Mutations in the Ornithine Transcarbamylase Gene Detected by Single-Strand Conformational Polymorphism. Pediatr Res 32, 600–604 (1992). https://doi.org/10.1203/00006450-199211000-00024
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DOI: https://doi.org/10.1203/00006450-199211000-00024
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