Nonsense-codon mutations of the ornithine aminotransferase gene with decreased levels of mutant mRNA in gyrate atrophy

Yukihiko Mashima, Akira Murakami, Richard G. Weleber, Nancy G. Kennaway, Lorne Clarke, Takashi Shiono, George Inana

Research output: Contribution to journalArticle

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Abstract

A generalized deficiency of the mitochondrial matrix enzyme ornithine aminotransferase (OAT) is the inborn error in gyrate atrophy (GA), an autosomal recessive degenerative disease of the retina and choroid of the eye. Mutations in the OAT gene show a high degree of molecular heterogeneity in GA, reflecting the genetic heterogeneity in this disease. Using the combined techniques of PCR, denaturing gradient gel electrophoresis, and direct sequencing, we have identified three nonsense-codon mutations and one nonsense codongenerating mutation of the OAT gene in GA pedigrees. Three of them are single-base substitutions, and one is a 2-bp deletion resulting in a reading frameshift. A nonsense codon created at position 79 (TGA) by a frameshift and nonsense mutations at codons 209 (TAT→TAA) and 299 (TAC→TAG) result in abnormally low levels of OAT mRNA in the patient's skin fibroblasts. A nonsense mutation at codon 426 (CGA→TGA) in the last exon, however, has little effect on the mRNA level. Thus, the mRNA level can be reduced by nonsense-codon mutations, but the position of the mutation may be important, with earlier premature-translation termination having a greater effect than a later mutation.

Original languageEnglish
Pages (from-to)81-91
Number of pages11
JournalAmerican Journal of Human Genetics
Volume51
Issue number1
StatePublished - Jul 1 1992

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Gyrate Atrophy
Ornithine-Oxo-Acid Transaminase
Nonsense Codon
Messenger RNA
Genes
Codon
Mutation
Choroid Diseases
Denaturing Gradient Gel Electrophoresis
Frameshift Mutation
Genetic Heterogeneity
Pedigree
Retina
Reading
Exons
Fibroblasts

ASJC Scopus subject areas

  • Genetics

Cite this

Nonsense-codon mutations of the ornithine aminotransferase gene with decreased levels of mutant mRNA in gyrate atrophy. / Mashima, Yukihiko; Murakami, Akira; Weleber, Richard G.; Kennaway, Nancy G.; Clarke, Lorne; Shiono, Takashi; Inana, George.

In: American Journal of Human Genetics, Vol. 51, No. 1, 01.07.1992, p. 81-91.

Research output: Contribution to journalArticle

Mashima, Y, Murakami, A, Weleber, RG, Kennaway, NG, Clarke, L, Shiono, T & Inana, G 1992, 'Nonsense-codon mutations of the ornithine aminotransferase gene with decreased levels of mutant mRNA in gyrate atrophy', American Journal of Human Genetics, vol. 51, no. 1, pp. 81-91.
Mashima, Yukihiko ; Murakami, Akira ; Weleber, Richard G. ; Kennaway, Nancy G. ; Clarke, Lorne ; Shiono, Takashi ; Inana, George. / Nonsense-codon mutations of the ornithine aminotransferase gene with decreased levels of mutant mRNA in gyrate atrophy. In: American Journal of Human Genetics. 1992 ; Vol. 51, No. 1. pp. 81-91.
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