宁夏地区苯丙酮尿症患儿苯丙氨酸羟化酶基因外显子6突变研究  

Research on mutations in exon 6 of phenylalanine hydroxylase gene in Ningxia childhood patients

作　　者：毛新梅 刘媛 何江 李晓强 余伍忠 

机构地区：[1]宁夏妇幼保健院儿童保健科,银川750004 [2]兰州军区乌鲁木齐总院临床医学研究所

出　　处：《中华实用儿科临床杂志》2014年第20期1568-1570,共3页Chinese Journal of Applied Clinical Pediatrics

基　　金：宁夏自然科学基金资助项目（NZ13237）

摘　　要：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.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.

关 键 词：苯丙氨酸羟化酶 基因突变 新突变 

分 类 号：R725.8[医药卫生—儿科]