title: An initiator codon mutation in ornithine-delta-aminotransferase causing gyrate atrophy of the choroid and retina.
abstract: 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.
authors.affiliation: Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: G A
authors.initials: GA
authors.lastname: Mitchell
authors.forename: L C
authors.initials: LC
authors.lastname: Brody
authors.forename: J
authors.initials: J
authors.lastname: Looney
authors.forename: G
authors.initials: G
authors.lastname: Steel
authors.forename: M
authors.initials: M
authors.lastname: Suchanek
authors.forename: C
authors.initials: C
authors.lastname: Dowling
authors.forename: V
authors.initials: V
authors.lastname: Der Kaloustian
authors.forename: M
authors.initials: M
authors.lastname: Kaiser-Kupfer
authors.forename: D
authors.initials: D
authors.lastname: Valle
mesh_terms: D002829:Choroid; D005128:Eye Diseases / Q000235:genetics*; D006801:Humans; D009154:Mutation; D009953:Ornithine-Oxo-Acid Transaminase / Q000172:deficiency / Q000235:genetics*; D010442:Peptide Chain Initiation, Translational; D012162:Retinal Degeneration / Q000235:genetics*; D000637:Transaminases / Q000235:genetics*
chemical_list: D000637:Transaminases; D009953:Ornithine-Oxo-Acid Transaminase