A European multicenter study of phenylalanine hydroxylase deficiency:: Classification of 105 mutations and a general system for genotype-based prediction of metabolic phenotype
A European multicenter study of phenylalanine hydroxylase deficiency:: Classification of 105 mutations and a general system for genotype-based prediction of metabolic phenotype
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DOI：
10.1086/301920
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发表时间：
1998-07-01
影响因子：
9.8
通讯作者：
Güttler, F
中科院分区：
文献类型：
--
作者：
Guldberg, P;Rey, F;Güttler, F
苯丙酮尿症(PKU)和轻度高苯丙氨酸血症(MHP)是由编码苯丙氨酸羟基酶(PAH)基因突变引起的等位基因紊乱。先前的研究表明，PAH缺乏症的高度可变的代谢表型与PAH基因型相关，我们在来自7个欧洲中心的686名患者中鉴定了这两种致病突变。根据297名功能性半合子患者的表型特征，105个突变被分配到四个任意表型类别中的一个。我们提出并测试了一个简单的模型，用于基因分型和表型结果之间的相关性。在79%的病例中，观察到的表型与预测的表型相符，而在184名患者中，只有5例观察到的表型与预期的表型相差超过一类。在七个贡献中心中，观察到的表型与预测表型不符的患者比例为4%-23%(P 10000)，这可能有助于新生儿高苯丙氨酸血症的治疗。
Phenylketonuria (PKU) and mild hyperphenylalaninemia (MHP) are allelic disorders caused by mutations in the gene encoding phenylalanine hydroxylase (PAH). Previous studies have suggested that the highly variable metabolic phenotypes of PAH deficiency correlate with PAH genotypes, We identified both causative mutations in 686 patients from seven European centers. On the basis of the phenotypic characteristics of 297 functionally hemizygous patients, 105 of the mutations were assigned to one of four arbitrary phenotype categories. We proposed and tested a simple model for correlation between genotype and phenotypic outcome. The observed phenotype matched the predicted phenotype in 79% of the cases, and in only 5 of 184 patients was the observed phenotype more than one category away from that expected. Among the seven contributing centers, the proportion of patients for whom the observed phenotype did not match the predicted phenotype was 4%-23% (P 10,000 genotypes, which may be useful for the management of hyperphenylalaninemia in newborns.