Hotta Y, Kennaway N G, Weleber R G, Inana G
National Eye Institute, Bethesda, MD 20892.
Am J Hum Genet. 1989 Mar;44(3):353-7.
We studied the human ornithine aminotransferase (OAT) gene, mRNA, and enzyme activity in fibroblasts from a family with gyrate atrophy (G.A.) of the choroid and retina, using a normal human OAT cDNA as a probe. The family consists of an affected patient, who is heterozygous for a partial deletion of the functional OAT gene and whose cells produce no mRNA, and of his father, mother, two sons, and a daughter. Southern blot analysis of the OAT gene showed the partial deletion in the patient and in his father and daughter and in one son. Northern blot analysis revealed no OAT mRNA in the patient and approximately 50% of the normal level of OAT mRNA in the father, mother, two sons, and daughter. Assay showed that the OAT activity in these individuals mirrored the OAT mRNA levels. The results indicate that an active allele of the OAT gene expresses 50% of the total normal OAT mRNA and activity and that both alleles of the gene are inactive in the patient in this pedigree, a situation resulting in a complete absence of the OAT mRNA, in accordance with the autosomal recessive mechanism of this disease; they also indicate a 50% decrease of OAT mRNA and enzyme activity in obligate heterozygous carriers carrying one defective allele and that these defects are stably inherited.
我们使用正常人鸟氨酸氨基转移酶（OAT）cDNA作为探针，研究了一个患有视网膜脉络膜回旋性萎缩（G.A.）的家族中，成纤维细胞里的人OAT基因、mRNA和酶活性。这个家族包括一名患病患者（其功能性OAT基因部分缺失且为杂合子，其细胞不产生mRNA）以及他的父亲、母亲、两个儿子和一个女儿。对OAT基因的Southern印迹分析显示，患者及其父亲、女儿和一个儿子存在部分缺失。Northern印迹分析表明，患者体内没有OAT mRNA，而其父亲、母亲、两个儿子和女儿体内的OAT mRNA水平约为正常水平的50%。检测显示，这些个体的OAT活性与OAT mRNA水平相符。结果表明，OAT基因的一个活性等位基因表达的OAT mRNA和活性占正常总量的50%，并且在这个家系的患者中该基因的两个等位基因均无活性，这种情况导致完全没有OAT mRNA，这与该疾病的常染色体隐性遗传机制一致；结果还表明，携带一个缺陷等位基因的必然杂合子携带者体内的OAT mRNA和酶活性降低了50%，且这些缺陷能够稳定遗传。
