探讨新疆南疆地区苯丙酮尿症(PKU)患儿苯丙氨酸羟化酶(PAH)基因第7，11，12外显子突变特征。

选择2009年3月至2013年12月在新疆南疆地区，经各级医疗机构确诊的42例PKU患儿(均于新生儿PKU筛查时即被确诊)为研究对象，采集其足跟血或静脉血，采用聚合酶链反应(PCR)产物直接测序法进行PAH基因第7，11，12外显子的基因突变分析。本研究遵循的程序符合新疆维吾尔自治区人民医院等各级医疗机构人体试验委员会制定的伦理学标准，得到该委员会批准，征得受试对象或其监护人知情同意，并与监护人签署临床研究知情同意书。

在42例患儿的42对PAH等位基因中，检测出7种PAH基因突变类型，共计46个PAH基因突变位点，其分别为：23个第7外显子c.735G>A(p.Val245Val)静默突变位点；8个第7外显子c.728G>A(p.Arg243Gln)错义突变位点；2个第7外显子c.781C>T(p.Arg261X)无义突变位点；1个第7外显子c.782G>A(p.Arg261Gln)错义突变位点；6个第11外显子c.1155G>C(p.Leu385Leu)静默突变位点；5个第12外显子c.1238G>C(p.Arg413Pro)错义突变位点及1个第12外显子c.1252A>C(p.Thr418Pro)错义突变位点。其中，第7外显子c.735G>A(p.Val245Val)突变位点占此次检出突变位点比例最高，为50.00%(23/46)，其突变频率为27.38%(23/84)。PAH基因的等位基因突变检出率为54.76%(46/84)。

新疆南疆地区PKU患儿PAH基因第7，11，12外显子的突变特征为：静默突变和错义突变为主要突变，第7外显子出现的突变类型和数量最多。

To study the characteristics of mutations of exon 7, 11, 12 in phenylalanine hydroxylase(PAH) gene of children with phenylketonuria(PKU) in south region of Xinjiang Uygur Autonomous Region.

A total of 42 children who made a definite diagnosis as PKU by different levels of medical institutions in the south region of Xinjiang by neonatal PKU screening from March 2009 to December 2013 were chosen as study subjects.The mutations of exon 7, 11, 12 of PAH gene were analyzed by detect heelstick blood or venous blood through polymerase chain reaction(PCR) and PAH gene DNA sequencing.The study protocol was approved by the Ethical Review Board of Investigation in Human Being of different levels of medical institutions in the south region of Xinjiang Uygur Autonomous Region, such as People's Hospital of Xingjiang Uygur Autonomous Region.Informed consent was obtained from the parents of each participant.

There were 7 types of mutation of PAH gene, and a total of 46 mutational sites were detected in 42 pairs of PAH alleles in 42 PKU children.There were 23 silent mutations of exon 7: c. 735G>A(p.Val245Val), 8 missense mutations of exon 7: c.728G>A(p.Arg243Gln), 2 nonsense mutations of exon 7: c. 781C>T(p.Arg261X), 1 missense mutations of exon 7: c.782G>A(p.Arg261Gln), 6 silent mutations of exon 11: c.1155G>C (p.Leu385Leu), 5 missense mutations of exon 12: c.1238G>C(p.Arg413Pro) and 1 missense mutation of exon 12: c.1252A>C(p.Thr418Pro). The exon 7: c.735G>A(p.Val245Val) mutational site has the highest detection ratio [50.00%(23/46)] in this study, and the mutation frequency was 27.38%(23/84). Mutation detection rate of PAH alleles was 54.76%(46/84).

The mutational characteristic in exon 7, 11, 12 of PAH gene in PKU children in south region of Xinjiang is silent mutational and missense mutation are major mutation types, and mutation types and amount of exon 7 are the most frequent.