An initiator codon mutation in ornithine-delta-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; D Valle

doi:10.1172/JCI113365

Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.

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Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.

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Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.

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Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.

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Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.

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Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.

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Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.

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Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.

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Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.

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Published in Volume 81, Issue 2 on February 1, 1988
J Clin Invest. 1988;81(2):630–633. https://doi.org/10.1172/JCI113365.
© 1988 The American Society for Clinical Investigation

Published February 1, 1988 - Version history

Gyrate atrophy of the choroid and retina (GA) is an autosomal recessive chorioretinal degeneration caused by deficiency of the mitochondrial matrix enzyme, ornithine-delta-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 truncate OAT by 138 amino acids, eliminating the entire mitochondrial leader sequence and 113 amino acids of the mature peptide.

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An initiator codon mutation in ornithine-delta-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, and D Valle

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An initiator codon mutation in ornithine-delta-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, and D Valle

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