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.

• PMID: 3339136
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Journal Article | Research Support, Non-U.S. Gov't | Research Support, U.S. Gov't, P.H.S.

Authors

Mitchell GA, Brody LC, Looney J, Steel G, Suchanek M, Dowling C, Der Kaloustian V, Kaiser-Kupfer M, Valle D

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