苯丙酮尿症患儿苯丙氨酸羟化酶exon6基因、exon7基因突变的研究  

Mutations in exon 6 and 7 of the phenylalanine hydroxylase(PAH) gene in chinese patients with phenylketonuria

作　　者：周永安[1] 李素云[1] 张改秀[2] 张全斌[1] 刘建平[3] 杨建萍[3] 王钰[1] 马云霞[1] 张晓刚[3] 郁梁[3] 

机构地区：[1]太原市中心医院中心实验室,030009 [2]山西省妇幼保健院内分泌科 [3]山西省妇幼保健院新生儿筛查中心

出　　处：《中华临床医师杂志（电子版）》2011年第1期221-224,共4页Chinese Journal of Clinicians(Electronic Edition)

基　　金：山西省科技攻关项目(20080311065);山西省卫生厅资助项目(200705)

摘　　要：目的探讨山西省苯丙酮尿症(PKU)患儿的苯丙氨酸羟化酶(PAH)exon6基因、exon7基因的突变特征。方法通过测序及序列比对的方法对56例PKU患儿和112例健康儿童的336个PAHexon6基因、exon7基因进行序列分析,以确定其突变位点、性质和频率。结果通过序列分析,发现在PKU患儿和健康儿童中均高频率的出现Q232Q(CAA→CAG)、V245V(GTG→GTA)两种同义突变,其中cDNA696位点的频率高达96.2%,cDNA735位点的频率高达76.1%。健康儿童的其他序列与Genbank完全相同。而PKU患儿的基因序列中还发现了9种共计37个突变基因,占全部PAH突变基因的33.04%。exon6仅发现一种突变基因Y204C,突变频率达9.8%;exon7中R243Q的突变率最高,占10.7%,其次为Ivs7+2T>A,占5.4%,其余的G247V、R252Q、L255S、R261Q、T278I和E280K分别占0.9%、0.9%、0.9%、0.9%、2.7%和0.9%。9种突变都在之前文献中有过报道,其中有7种错义突变和2种剪接位点突变。结论明确了PAH exon6基因、exon7基因的突变种类和分布等特征,表明exon6基因、exon7基因中Y204C和R243Q属于山西人群中PAH基因突变的热点。Objective To study mutation in exon 6 and 7 of the gene for the phenylalanine hydroxylase （PAH）.Methods The mutations in exon 6 and 7 and flanking sequence of PAH gene were detected by DNA sequencing,involved in 56 patients with phenylketonuria and112 healthy kids.Results Two synonymous mutations-Q232Q （CAA→CAG） and V245V （GTG→GTA） were also detected,which the frequency of cDNA 696 mutation G type and cDNA735-A point mutation was respectively up to 96.2% and 76.1%,we concluded that the 696 735 wild-type site may be G,A in Shanxi Province. Besides,thirty-seven different mutations account for 33.04% of mutant alleles,Y204C was found in exon6; In exon 7,R243Q was the highest incidence,accounting for 10.7%,followed by Ivs7 ＋ 2 TA,5.4%,G247V,R252Q,L255S,R261Q,T278I and E280K accounting for 0.9%,0.9%,0.9%,0.9%,2.7%,0.9% respectively. 7 missense mutations and 2 splice site mutation were included in 9 kinds of different mutations.Conclusions The mutation characteristics and distribution in exon 6 and 7 of PAH gene has been identified,which showed that the Y204C and R243Q were the hot region of PAH gene mutation in Shanxi PKU population.

关 键 词：苯丙酮尿症 苯丙氨酸羟化酶 突变 序列分析 外显子 

分 类 号：R725.8[医药卫生—儿科]