Kozák L, Kuhrová V, Blazková M, Romano V, Fajkusová L, Dvoráková D, Pijácková A
Research Institute of Child Health, Department of Biochemical and Molecular Genetics, Czech Republic.
Hum Genet. 1995 Oct;96(4):472-6. doi: 10.1007/BF00191809.
A detailed study of the mutant phenylalanine hydroxylase (PAH) gene from the eastern part of the Czech Republic (Moravia) is reported. A total of 190 mutant alleles from 95 phenylketonuria (PKU) families were analyzed for 21 prevalent Caucasian mutations and restriction fragment length polymorphism/variable number of tandem repeats (RFLP/VNTR) haplotypes. Eighty per cent of all mutant alleles were found to carry 11 mutations. The most common molecular defect was the mutation R408W (55.3%), with a very high degree of homozygosity (34.6%). Each of four other mutations (R158Q, R243X, G272X, IVS12nt1) accounted for more than 3% of PKU alleles. Rarely present were mutations IVS10nt546 (2.6%), R252W (2.6%), L48S (2.1%), R261Q (1.6%), Y414C (1.0%) and 165T (0.5%). Mutations that have been predominantly described in southern Europe (IVS7nt1, A259V, Y277D, R241H, T278N) were not detected. A total of 14 different mutant haplotypes were observed. Three unusual genotype-haplotype associations were identified (R158Q on haplotypes 2.3 and 7.8 and R252W on haplotype 69.3). There was a strong association between the mutation R408W and haplotype 2.3 (54.7%). Heterogeneity was found at mutations R408W (haplotypes 2.3 and 5.9), R158Q (haplotypes 4.3, 2.3 and 7.8) and IVS10nt546 (haplotypes 6.7 and 34.7). The molecular basis of PKU in the Moravian area appears to be relatively homogeneous in comparison with other southern and western European populations, thus providing a good starting point for prenatal diagnosis and early clinical classification.
本文报道了对来自捷克共和国东部（摩拉维亚）的突变型苯丙氨酸羟化酶（PAH）基因的详细研究。对95个苯丙酮尿症（PKU）家庭的190个突变等位基因进行了分析，检测了21种常见的高加索人突变以及限制性片段长度多态性/可变串联重复序列（RFLP/VNTR）单倍型。发现所有突变等位基因中有80%携带11种突变。最常见的分子缺陷是R408W突变（55.3%），纯合度非常高（34.6%）。其他四种突变（R158Q、R243X、G272X、IVS12nt1）每种在PKU等位基因中所占比例均超过3%。IVS10nt546（2.6%）、R252W（2.6%）、L48S（2.1%）、R261Q（1.6%）、Y414C（1.0%）和165T（0.5%）突变很少出现。在南欧主要报道的突变（IVS7nt1、A259V、Y277D、R241H、T278N）未被检测到。共观察到14种不同的突变单倍型。鉴定出三种不寻常的基因型 - 单倍型关联（单倍型2.3和7.8上的R158Q以及单倍型69.3上的R252W）。R408W突变与单倍型2.3之间存在强关联（54.7%）。在R408W（单倍型2.3和5.9）、R158Q（单倍型4.3、2.3和7.8）和IVS10nt546（单倍型6.7和34.7）突变处发现了异质性。与其他南欧和西欧人群相比，摩拉维亚地区PKU的分子基础似乎相对均匀，因此为产前诊断和早期临床分类提供了一个良好的起点。
