Centre for Human Metabonomics, School for Physical and Chemical Sciences, North-West University, Potchefstroom, 2520, South Africa.
Gene. 2012 Mar 1;495(1):56-61. doi: 10.1016/j.gene.2011.12.021. Epub 2011 Dec 23.
The autosomal recessive disorder, hereditary tyrosinemia type 1 (HT1), is caused by a defective fumarylacetoacetate hydrolase enzyme. Consequently intermediate metabolites such as fumarylacetoacetate, succinylacetone and p-hydroxyphenylpyruvic acid accumulate. Characteristic to HT1 is the development of hepatocellular carcinoma, irrespective of dietary intervention or pharmacological treatment. Carcinogenesis may occur through a chromosomal instability mutator phenotype or a microsatellite instability phenotype, and deficient DNA repair may be a contributing factor thereof. The purpose of this study was to investigate the expression of DNA repair proteins, and the possible occurrence of microsatellite instability in HT1. Gene expression analyses show low expression of hOGG1 and ERCC1 in HT1 patient lymphocytes. Results from microsatellite instability analyses show allelic imbalance on chromosome 7 of the fah(-/-) mouse genome, and instability of the D2S123, D5S346 and (possibly) D17S250 microsatellite markers, in HT1 patient lymphocytes.
常染色体隐性遗传疾病 1 型遗传性酪氨酸血症（HT1）是由缺陷的延胡索酰乙酰乙酸水解酶引起的。因此，中间代谢产物如延胡索酰乙酰乙酸、丁二酮和对羟苯丙酮酸会积累。HT1 的特征是无论饮食干预还是药物治疗，都会发展为肝细胞癌。癌变可能通过染色体不稳定突变表型或微卫星不稳定性表型发生，并且 DNA 修复缺陷可能是其促成因素之一。本研究旨在研究 DNA 修复蛋白的表达，以及 HT1 中可能发生的微卫星不稳定性。基因表达分析显示 HT1 患者淋巴细胞中 hOGG1 和 ERCC1 的表达水平较低。微卫星不稳定性分析结果显示 fah(-/-) 小鼠基因组 7 号染色体上存在等位基因失衡，以及 HT1 患者淋巴细胞中 D2S123、D5S346 和（可能）D17S250 微卫星标记的不稳定性。
