Rootwelt H, Chou J, Gahl W A, Berger R, Coşkun T, Brodtkorb E, Kvittingen E A
Institute of Clinical Biochemistry, University of Oslo, Rikshospitalet, Norway.
Hum Genet. 1994 Jun;93(6):615-9. doi: 10.1007/BF00201558.
Hereditary tyrosinemia type 1, due to a deficiency of fumarylacetoacetase (FAH), is characterized by progressive liver damage and renal tubular dysfunction and may occur in an acute or a chronic form. An Ala 134 to Asp (GCT to GAT) transition was found in one Turkish and two Norwegian patients with chronic tyrosinemia. SphI digestion of polymerase chain reaction (PCR) amplified genomic DNA identified the mutation and showed that the patients were heterozygous. All these patients had immunoreactive FAH protein in fibroblasts. Another Norwegian patient with chronic disease, without FAH immunoreactive material in fibroblasts, had a Pro 342 to Leu mutation (CCG to CTG). This mutation was identified by MspI digestion of PCR amplified genomic DNA, and the patient was heterozygous. Northern blotting showed FAH mRNA of normal size and amounts in all patients. Site directed mutagenesis and translation in a rabbit reticulocyte lysate demonstrated that both mutations abolished FAH activity.
1型遗传性酪氨酸血症是由于延胡索酰乙酰乙酸酶（FAH）缺乏所致，其特征为进行性肝损伤和肾小管功能障碍，可呈急性或慢性形式。在一名土耳其和两名挪威慢性酪氨酸血症患者中发现了丙氨酸134突变为天冬氨酸（GCT突变为GAT）。聚合酶链反应（PCR）扩增的基因组DNA经SphI酶切鉴定出该突变，并显示患者为杂合子。所有这些患者的成纤维细胞中都有免疫反应性FAH蛋白。另一名患有慢性疾病的挪威患者，其成纤维细胞中没有FAH免疫反应性物质，发生了脯氨酸342突变为亮氨酸（CCG突变为CTG）。该突变通过PCR扩增的基因组DNA经MspI酶切鉴定，患者为杂合子。Northern印迹法显示所有患者的FAH mRNA大小和数量正常。定点诱变和兔网织红细胞裂解物中的翻译表明，这两种突变均消除了FAH活性。
