摘要目的 了解河南地区苯丙酮尿症患者苯丙氨酸羟化酶(phenylalanine hydroxylase,PAH)基因的变异规律及特点.方法 应用聚合酶链反应对113例苯丙酮尿症家系的先证者PAH基因全部13个外显子进行测序检测,同时应用多重连接探针扩增技术检测PAH基因是否存在大片段缺失重复.结果 113例先证者共226个等位基因共检出195个变异位点及3个大片段缺失重复,检出率分别为86.28％ 和1.33％.检出率较高的变异位点分别为p.Arg243Gln(18.14％)、p.Arg111X(6.19％)、p.Arg53 His(5.31％)、EX6-96A>G(5.31％)、p.Tyr356X(4.87％)及p.Val399Val(4.42％).变异频率较高的外显子分别为第7、11、3及6外显子.错义变异为最常见的类型.其中c.1016C>A(p.Ser339Tyr)、c.1000T>C(p.Cys334Arg)、c.1110G>T(p.Glu370Asp)和IVS6+1G>T为未报道过的新变异.结论 河南省PAH基因的变异种类较多,存在广泛的等位基因异质性.

abstractsObjective To explore the characteristics of PAH gene variants among 113 phenylketonuria patients from Henan Province.Methods The 13 exons of the PAH gene were subjected to PCR amplification and direct sequencing.Large fragment deletion and duplication of the PAH gene were detected with a multiple ligation-dependent probe amplification (MLPA)assay.Results In total 195 point variants and 3 large fragment deletions were detected among the 226 alleles,with the detection rates being 86.28％ and 1.33％,respectively.Variants of p.Arg243Gln (18.14％),p.Arg111X (6.19％),Arg53 His (5.31％),EX6-96A > G (5.31％),p.Tyr356X (4.87％)and p.Val399Val (4.42％)were relatively common.Most of the variants were located in exons 7,11,3 and 6.Missense variations were most common.Four novel variations were detected,which included c.1016C>A (p.Ser339Tyr),c.1000T>C (p.Cys334Arg),c.1110G>T (p.Glu370Asp),and IVS6+1G>T.Conclusion The PAH gene variations in Henan Province have featured extensive allelic heterogeneity and variety.