Rootwelt H, Høie K, Berger R, Kvittingen E A
Institute of Clinical Biochemistry, University of Oslo, Rikshospitalet, Norway.
Hum Mutat. 1996;7(3):239-43. doi: 10.1002/(SICI)1098-1004(1996)7:3<239::AID-HUMU8>3.0.CO;2-5.
Sixty-two hereditary tyrosinaemia type I (HT1) patients of various ethnic origins were classified clinically into acute, chronic, or intermediate phenotypes and screened for the 14 published causal mutations in the fumarylacetoacetase (FAH) gene. Restriction analysis of PCR amplified genomic DNA identified 74% of the mutated alleles. IVS12 + 5G --> A, predominant in the French Canadian HT1 patients, was the most common mutation found in 32 alleles in patients from Europe, Pakistan, Turkey, and the United States. IVS6-1G --> T, encountered in 14 alleles, was common in Central and Western Europe. There was an apparent "Scandinavian" 1009G --> A combined splice and missense mutation (12 alleles), a "Pakistani" 192G --> T splice mutation (11 alleles), a "Turkish" D233V mutation (6 alleles), and a "Finnish" or northern European W262X mutation (7 alleles). The remaining mutations were rare. Some of the mutations seem to predispose for acute and other for more chronic forms of HT1, but in our material no clearcut genotype phenotype correlation could be established.
62例不同种族来源的遗传性I型酪氨酸血症（HT1）患者按临床分为急性、慢性或中间型表型，并对延胡索酰乙酰乙酸酶（FAH）基因中已发表的14种致病突变进行筛查。对聚合酶链反应（PCR）扩增的基因组DNA进行限制性分析，鉴定出74%的突变等位基因。IVS12 + 5G→A在法裔加拿大HT1患者中占主导地位，是在来自欧洲、巴基斯坦、土耳其和美国的患者中发现的32个等位基因中最常见的突变。IVS6 - 1G→T在14个等位基因中出现，在中欧和西欧很常见。有一个明显的“斯堪的纳维亚”1009G→A联合剪接和错义突变（12个等位基因）、一个“巴基斯坦”192G→T剪接突变（11个等位基因）、一个“土耳其”D233V突变（6个等位基因）和一个“芬兰”或北欧W262X突变（7个等位基因）。其余突变较为罕见。一些突变似乎易导致急性HT1，而另一些则易导致更慢性的形式，但在我们的研究材料中，无法建立明确的基因型-表型相关性。
