Advertisement
Research Article Free access | 10.1172/JCI113365
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Find articles by Mitchell, G. in: JCI | PubMed | Google Scholar
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Find articles by Brody, L. in: JCI | PubMed | Google Scholar
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Find articles by Looney, J. in: JCI | PubMed | Google Scholar
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Find articles by Steel, G. in: JCI | PubMed | Google Scholar
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Find articles by Suchanek, M. in: JCI | PubMed | Google Scholar
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Find articles by Dowling, C. in: JCI | PubMed | Google Scholar
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Find articles by Der Kaloustian, V. in: JCI | PubMed | Google Scholar
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Find articles by Kaiser-Kupfer, M. in: JCI | PubMed | Google Scholar
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Find articles by Valle, D. in: JCI | PubMed | Google Scholar
Published February 1, 1988 - More info
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.
Images.
Click on an image below to see the page. View PDF of the complete article