A deletion in the ornithine aminotransferase gene in gyrate atrophy

Yasushi Akaki, Yoshihiro Hotta, Yukihiko Mashima, Akira Murakami, Nancy G. Kennaway, Richard Weleber, George Inana

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Gyrate atrophy (GA) is an autosomal recessive chorioretinal degenerative disease of the eye caused by an inborn defect of the nuclear encoded mitochondrial enzyme ornithine aminotransferase (OAT). We have described previously a GA patient with a 5.0-kilobase pair truncated EcoRI OAT gene fragment and the absence of OAT mRNA on Northern blot analysis. Cloning and sequencing analysis of the truncated gene fragment revealed a 1,072-base pair (bp) deletion including the entire exon 6, starting in intron 5, 172 bp upstream of exon 6 and ending in intron 6, 772 bp downstream of exon 6. A short direct repeat sequence (AGGAGC), resembling the sequence shown to cause DNA polymerase α to pause, and sequences capable of forming hairpin loops were both present at the 5′ and 3′ breakpoints of the deletion. Reverse transcription-polymerase chain reaction amplification of the patient's RNA with OAT primers yielded DNA fragments of two different sizes, consistent with a low level expression of OAT mRNA. Direct sequencing of the smaller fragment demonstrated the complete absence of exon 6 sequence in the mRNA predicted from the deletion, causing a reading frame shift which results in a premature termination codon at position 192. The mutation in the other allele has been demonstrated by polymerase chain reaction, denaturing gradient gel electrophoresis, and direct sequencing also to be a premature termination codon in exon 6. The absence of detectable OAT mRNA in this patient is consistent with these premature termination mutations because they have been shown to decrease the level of mRNA, especially if present early in the coding sequence.

Original languageEnglish (US)
Pages (from-to)12950-12954
Number of pages5
JournalJournal of Biological Chemistry
Volume267
Issue number18
StatePublished - Jun 25 1992

Fingerprint

Gyrate Atrophy
Ornithine-Oxo-Acid Transaminase
Genes
Exons
Messenger RNA
Base Pairing
Nonsense Codon
Polymerase chain reaction
Introns
Reading Frames
Polymerase Chain Reaction
Denaturing Gradient Gel Electrophoresis
Mutation
DNA Primers
Eye Diseases
Nucleic Acid Repetitive Sequences
Cloning
DNA-Directed DNA Polymerase
Transcription
Electrophoresis

ASJC Scopus subject areas

  • Biochemistry

Cite this

Akaki, Y., Hotta, Y., Mashima, Y., Murakami, A., Kennaway, N. G., Weleber, R., & Inana, G. (1992). A deletion in the ornithine aminotransferase gene in gyrate atrophy. Journal of Biological Chemistry, 267(18), 12950-12954.

A deletion in the ornithine aminotransferase gene in gyrate atrophy. / Akaki, Yasushi; Hotta, Yoshihiro; Mashima, Yukihiko; Murakami, Akira; Kennaway, Nancy G.; Weleber, Richard; Inana, George.

In: Journal of Biological Chemistry, Vol. 267, No. 18, 25.06.1992, p. 12950-12954.

Research output: Contribution to journalArticle

Akaki, Y, Hotta, Y, Mashima, Y, Murakami, A, Kennaway, NG, Weleber, R & Inana, G 1992, 'A deletion in the ornithine aminotransferase gene in gyrate atrophy', Journal of Biological Chemistry, vol. 267, no. 18, pp. 12950-12954.
Akaki Y, Hotta Y, Mashima Y, Murakami A, Kennaway NG, Weleber R et al. A deletion in the ornithine aminotransferase gene in gyrate atrophy. Journal of Biological Chemistry. 1992 Jun 25;267(18):12950-12954.
Akaki, Yasushi ; Hotta, Yoshihiro ; Mashima, Yukihiko ; Murakami, Akira ; Kennaway, Nancy G. ; Weleber, Richard ; Inana, George. / A deletion in the ornithine aminotransferase gene in gyrate atrophy. In: Journal of Biological Chemistry. 1992 ; Vol. 267, No. 18. pp. 12950-12954.
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