Nonsense-codon mutations of the ornithine aminotransferase gene with decreased levels of mutant mRNA in gyrate atrophy.

摘要: A generalized deficiency of the mitochondrial matrix enzyme ornithine aminotransferase (OAT) is inborn error in gyrate atrophy (GA), an autosomal recessive degenerative disease retina and choroid eye. Mutations OAT gene show a high degree molecular heterogeneity GA, reflecting genetic this disease. Using combined techniques PCR, denaturing gradient gel electrophoresis, direct sequencing, we have identified three nonsense-codon mutations one nonsense codon-generating mutation GA pedigrees. Three them are single-base substitutions, 2-bp deletion resulting reading frameshift. codon created at position 79 (TGA) by frameshift codons 209 (TAT----TAA) 299 (TAC----TAG) result abnormally low levels mRNA patient's skin fibroblasts. 426 (CGA----TGA) last exon, however, has little effect on level. Thus, level can be reduced mutations, but may important, with earlier premature-translation termination having greater than later mutation.