St-Louis M, Tanguay R M
Laboratoire de Génétique Cellulaire et Développementale, RSVS, Université Laval, Ste-Foy (Québec), Canada.
Hum Mutat. 1997;9(4):291-9. doi: 10.1002/(SICI)1098-1004(1997)9:4<291::AID-HUMU1>3.0.CO;2-9.
Tyrosinemia type I is an inborn error of metabolism caused by a deficiency in the last enzyme of the tyrosine catabolic pathway, fumarylacetoacetate hydrolase (FAH). The disease has been reported worldwide with varying incidence. Recently, there has been considerable progress in identifying mutations in the FAH gene. At present 26 mutations have been reported, all consisting of single base substitutions resulting in 16 amino acid replacements, one silent mutation causing a splicing defect, five nonsense codons, and four putative splicing defects. The location of these mutations is spread over the entire FAH gene, with a particular clustering between amino acid residues 230 and 250. The identification of these mutations in subpopulations and groups at high risk should help in the diagnosis of, and genetic counseling for, HT1. We describe all these 26 mutations reported so far and their implication in diagnosis and carrier detection.
I型酪氨酸血症是一种先天性代谢缺陷病，由酪氨酸分解代谢途径中的最后一种酶——富马酰乙酰乙酸水解酶（FAH）缺乏所致。该病在全球均有报道，发病率各异。最近，在鉴定FAH基因突变方面取得了相当大的进展。目前已报道了26种突变，均为单碱基替换，导致16个氨基酸替换、1个导致剪接缺陷的沉默突变、5个无义密码子和4个推定的剪接缺陷。这些突变的位置分布在整个FAH基因上，在氨基酸残基230至250之间有特别的聚集。在亚群体和高危人群中鉴定这些突变应有助于I型酪氨酸血症的诊断和遗传咨询。我们描述了迄今为止报道的所有这26种突变及其在诊断和携带者检测中的意义。
