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

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PAH exon6 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cDNA 696 位点的频率高达96.2%,cDNA 735 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%.exon 6 仅发现一种突变基因Y204C,突变频率达9.8%;exon 7 中R243Q 的突变率最高,占10.7%,其次为Ivs7 +2 T ＞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.

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

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.