Jaruzelska J, Matuszak R, Lyonnet S, Rey F, Rey J, Filipowicz J, Borski K, Munnich A
Institute of Human Genetics, Polish Academy of Sciences, Poznań.
J Med Genet. 1993 Mar;30(3):232-4. doi: 10.1136/jmg.30.3.232.
In order to elucidate the clinical homogeneity and severity of the hyperphenylalaninaemias in Poland, a total of 71 children with typical phenylketonuria (PKU) originating from western and northern Poland were screened for 13 mutations in the phenylalanine hydroxylase (PAH) gene. Eighty percent of all PKU alleles tested were found to carry an identified mutation. One mutation, namely the R408W mutation, accounted for more than 63% of mutant PAH alleles in Poland, the other 27% being accounted for by six mutations: IVS12nt1 (5%), IVSnt546 (5%), Y414C (4%), R252W (1.5%), R261Q (< 1%), and G272ter (< 1%). The predominance of the R408W mutation resulted in a high rate of homozygotes (35.2%) and compound heterozygotes for this mutation in children from western and northern Poland. The frequency and deleterious nature of this mutation probably accounts for the clinical homogeneity and severity of the hyperphenylalaninaemias in Poland. In addition, the high rate of the R408W mutation and its association with mutant haplotype 2 at the PAH locus in Poland give additional support to the Balto-Slavic origin of this mutant gene.
为了阐明波兰高苯丙氨酸血症的临床同质性和严重程度，对来自波兰西部和北部的71例典型苯丙酮尿症（PKU）患儿进行了苯丙氨酸羟化酶（PAH）基因13种突变的筛查。在所有检测的PKU等位基因中，80%发现携带已识别的突变。一种突变，即R408W突变，占波兰突变型PAH等位基因的63%以上，其他27%由六种突变组成：IVS12nt1（5%）、IVSnt546（5%）、Y414C（4%）、R252W（1.5%）、R261Q（<1%）和G272ter（<1%）。R408W突变的优势导致波兰西部和北部儿童中该突变的纯合子（35.2%）和复合杂合子比例很高。这种突变的频率和有害性质可能解释了波兰高苯丙氨酸血症的临床同质性和严重程度。此外，波兰R408W突变的高发生率及其与PAH基因座突变单倍型2的关联，进一步支持了该突变基因的波罗的-斯拉夫起源。
