CAJ | 학술논문

目的探讨宁夏地区苯丙酮尿症(PKU)患儿苯丙氨酸羟化酶(PAH)基因外显子6突变类型及频率,为该地区PKU的基因诊断和产前诊断提供依据.方法应用聚合酶联反应(PCR)产物直接测序方法,对宁夏73例经典型PKU患儿[PKU患儿均为宁夏新生儿疾病筛查中心2010年1月至2013年6月确诊,病例分布于宁夏22县(市、区);年龄15 d～13岁;男38例,女35例;回族39例,汉族34例]和100例(回族50例,汉族50例)健康新生儿的PAH基因外显子6及其旁侧内含子区域进行序列分析.结果共检测出6种基因突变型别,分别是EX6-96A＞ G(6.85％)、Q232X(2.74％)、D222G(1.37％)、V2301(1.37％)、R176X(0.68％)和N223I(0.68％),基因外显子6突变检出率为13.70％,包括3种突变型别,分别是错义突变3种(50.0％)、无义突变2种(33.3％)和剪切位点突变1种(16.7％);查阅国内外文献,其中EX6-96A＞G、Q232X和R176X国内早有报道,D222G、V2301为国内首次报道的PAH突变,N223I为国际上尚未见报道的新PAH突变.结论明确了宁夏地区PAH基因外显子6突变类型及频率,丰富了该地区PKU基因研究,为开展PKU的基因诊断提供依据.
목적 탐토저하지구분병동뇨증(PKU)환인분병안산간화매(PAH)기인외현자6돌변류형급빈솔,위해지구PKU적기인진단화산전진단제공의거.방법 응용취합매련반응(PCR)산물직접측서방법,대저하73례경전형PKU환인[PKU환인균위저하신생인질병사사중심2010년1월지2013년6월학진,병례분포우저하22현(시、구);년령15 d～13세;남38례,녀35례;회족39례,한족34례]화100례(회족50례,한족50례)건강신생인적PAH기인외현자6급기방측내함자구역진행서렬분석.결과 공검측출6충기인돌변형별,분별시EX6-96A＞ G(6.85％)、Q232X(2.74％)、D222G(1.37％)、V2301(1.37％)、R176X(0.68％)화N223I(0.68％),기인외현자6돌변검출솔위13.70％,포괄3충돌변형별,분별시착의돌변3충(50.0％)、무의돌변2충(33.3％)화전절위점돌변1충(16.7％);사열국내외문헌,기중EX6-96A＞G、Q232X화R176X국내조유보도,D222G、V2301위국내수차보도적PAH돌변,N223I위국제상상미견보도적신PAH돌변.결론 명학료저하지구PAH기인외현자6돌변류형급빈솔,봉부료해지구PKU기인연구,위개전PKU적기인진단제공의거.
Objective To understand the type and frequency of the gene mutation in exon 6 of phenylalanine hydroxylase(PAH) in the children of Ningxia,in order to provide foundation for phenylketonuria(PKU) gene diagnosis and prenatal diagnosis.Methods The exon 6 and flanking introns of 73 cases of classic PKU patients in Ningxia[all confirmed at Ningxia Neonatal Screening Center from Jan.2010 to Jun.2013,and distributed in Ningxia 22 County (city,district),aged from 15 days to 13 years,including 38 male cases,35 female cases,and Hui 39 cases,Han 34 cases] as well as 100 healthy newborn babies(Hui 50 cases;Han 50 cases) were sequentially analyzed by using the approach of PCR direct sequencing.Results There were 6 kinds of mutations detected,including EX6-96A ＞ G(6.85％),Q232X(2.74％),D222G(1.37％),V2301 (1.37％),R176X (0.68％) and N223I (0.68％).Mutation detection rate of exon 6 was 13.70％,and there were 3 mutation types:50.0％ missense mutation (3 types) ;33.3 ％ nonsense mutation (2 types) ;16.7％ cleavage site mutation(1 type).After reviewing the previous studies,the researchers had found out that EX6-96A ＞ G,Q232X and R176X were ever reported in China,and V2301 and D222G had been reported in our country for the first time but N223I was a new kind of PAH gene mutations were not been reported in the world.Conclusions It has defined the gene type and frequency of PAH gene mutations in exon 6 in the children of Ningxia and it will enrich the research of PKU in this area,and provide the basis for the development of gene diagnosis of PKU.