An initiator codon mutation in ornithine-δ-aminotransferase causing gyrate atrophy of the choroid and retina

G. A. Mitchell, L. C. Brody, J. Looney, G. Steel, M. Suchanek, C. Dowling, V. Der Kaloustian, M. Kaiser-Kupfer, David Valle

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Abstract

Gyrate atrophy of the choroid and retina (GA) is an autosomal recessive chorioretinal degeneration caused by deficiency of the mitochondrial matrix enzyme, ornithine-δ-aminotransferase (OAT). To study the molecular basis of the mutations causing GA, we cloned and sequenced the human OAT cDNA and determined the intron-exon arrangement of the structural gene. Using the cDNA template, we synthesized antisense RNA probes and performed RNase A protection experiments with RNA from four Lebanese GA patients. We found a probe-target mismatch at the 5' end of the first coding exon and amplified this region of the patients' genomic DNA using the polymerase chain reaction. Sequence analysis showed a G → A transition, changing the initiator ATG (methionine) codon to ATA. This mutation segregates with the GA allele in both pedigrees. Initiation of translation at the closest in-frame methionine codon would truncage OAT by 138 amino acids, eliminating the entire mitochondrial leader sequence and 113 amino acids of the mature peptide.

Original languageEnglish (US)
Pages (from-to)630-633
Number of pages4
JournalJournal of Clinical Investigation
Volume81
Issue number2
Publication statusPublished - 1988

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ASJC Scopus subject areas

  • Medicine(all)

Cite this

Mitchell, G. A., Brody, L. C., Looney, J., Steel, G., Suchanek, M., Dowling, C., ... Valle, D. (1988). An initiator codon mutation in ornithine-δ-aminotransferase causing gyrate atrophy of the choroid and retina. Journal of Clinical Investigation, 81(2), 630-633.