摘要目的 探讨广西地区苯丙酮尿症( PKU)患儿苯丙氨酸羟化酶( PAH)基因突变特征,为遗传咨询和产前基因诊断提供依据.方法 选取2009 年1 月至2017 年12 月在广西壮族自治区妇幼保健院确诊为PKU的37例患儿为研究对象,采集静脉血3 mL,采用聚合酶链反应技术扩增PAH基因,并采用Sanger测序法对患儿及其父母的PAH基因1~13外显子及其侧翼内含子区域进行基因测序分析.检索国内外相关文献及数据库判断发现的基因突变是否为新突变,同时通过检测100例健康个体为对照组进行基因测序,以证实该突变是否为新突变.结果 37例PKU共检测出68个突变位点,突变检出率为91. 89%(68／74个),第7外显子为高频突变区域,包含6 种突变,相对突变频率为31. 08%,其次为第12 外显子( 18. 92%)、第8 外显子(10. 81%)及第6外显子(10. 81%);共检出PAH基因突变25种,包括错义突变14种(56. 00%)、无义突变7种(28. 00%)、剪接突变3种(12. 00%)、缺失突变1种(4. 00%).其中c. 1223G＞A(p. R408Q)、c. 728G＞A (p. R243Q)、c. 721C＞T(p. R241C)为热点突变,分别占总突变频率的14. 86%、13. 51%、10. 81%.3 种突变c. 314C＞T(p. T105I)、c. 583A＞G(p. K195E)、c. 851G＞A( p. C284Y)经国际PAH突变数据库和人类基因突变数据库等数据库比对查新及软件预测,为未报道的PAH基因新突变.结论 初步获得广西地区的PAH基因突变图谱,发现3种新突变,为本地区PKU基因诊断、产前诊断积累有价值的资料.

abstractsObjective To investigate the characteristics of the phenylalanine hydroxylase( PAH)gene muta﹣tions in patients With phenylketonuria(PKU)in Guangxi region,in order to provide clinical data for genetic counseling and prenatal gene diagnosis. Methods Thirty－seven children diagnosed as PKU in the Maternal and Children＇s Hos﹣pital of Guangxi Zhuang Autonomous Region Were enrolled in the study betWeen January 2009 and December 2017. Ve﹣nous blood Was collected and the PAH gene sequence Was determined by Sanger sequencing after amplification With the polymerase chain reaction technique. The neW gene mutations Were defined based on the national and international literature revieW and databases. MeanWhile,100 healthy individuals Were selected as the control group for gene sequen﹣cing to confirm Whether the mutation Was a neW one. Results Thirty－seven cases of PKU Were detected for 68 muta﹣tions,With the detection rate being 91. 89%(68／74). Six mutations Were identified in exon 7,Which accounted for 31. 08% of all,exon 12(18. 92%),exon 8(10. 81%)and exon 6(10. 81%)folloWed. A total of 25 different muta﹣tions Were identified Which including 14 missense mutations(56. 00%),7 nonsense mutations(28. 00%),3 splicing junction mutations(12. 00%),and 1 deletion mutation(4. 00%). The most common mutations included c. 1223G＞A (p. R408Q),c. 728G＞A(p. R243Q)and c. 721C＞T( p. R241C),accounting for 14. 86%,13. 51%,and 10. 81%, respectively. After querying international databases,including PAH mutation database and Human Gene Mutation Data﹣base and forecasting softWare,three kinds of mutations c. 314C＞ T(p. T105I),c. 583A＞ G(p. K195E),c . 851G＞A(p. C284Y)Were verified as novel PAH gene mutations. Conclusions The mutation spectrum of the PAH gene in Guangxi has been identified. And 3 kinds of mutations have been identified. This may accumulate valuable information for gene diagnosis and prenatal diagnosis of PKU in Guangxi region.