Mutational Spectrum of Phenylketonuria in the Chinese Han Population: A Novel Insight into the Geographic Distribution of the Common Mutations
Mutational Spectrum of Phenylketonuria in the Chinese Han Population: A Novel Insight into the Geographic Distribution of the Common Mutations
复制标题
中国汉族人群苯丙酮尿症突变谱：对常见突变地理分布的新见解
DOI：
10.1203/pdr.0b013e3181c9fb85
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发表时间：
2010-03-01
影响因子：
3.6
通讯作者：
Gu, Xuefan
中科院分区：
文献类型：
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作者：
Zhu, Tianwen;Qin, Shengying;Gu, Xuefan
由于缺乏对中国汉族人群苯丙酮尿症 (PKU) 突变的全面分析，过去 18 年中，人们不断进行研究，以阐明几乎所有中国地区患者的突变谱。我们的研究使用 PCR 和直接测序系统地研究了 212 名无关患者的苯丙氨酸羟化酶 (PAH) 基因的 13 个外显子及其周围的内含子。在 424 个突变 PAH 等位基因中的 405 个中总共鉴定出 79 个不同的突变，其中包括 15 个新突变。 R243Q、Ex6–96A>G、IVS4 − 1G>A、R413P、Y356X、R111X、R241C 和 V399V 8 个突变，相对频率为 3% 或更高，占已识别突变的三分之二。本研究提供的数据表明，中国的突变型 PAH 等位基因总数由少量常见突变和大量罕见突变组成。此外，通过合并之前的研究结果，生成更综合的中国大陆数据集，结果显示，除了R413P之外，南方和北方的常见突变在统计上没有显着差异，这对之前关于上述地区之间突变频率存在巨大差异的假设提出了质疑。
The absence of a comprehensive analysis for phenylketonuria (PKU) mutations in the Chinese Han population has resulted in continued studies during the past 18 y to elucidate the mutational spectrum in patients from virtually all Chinese regions. Our study systematically investigated 13 exons and their surrounding introns of the phenylalanine hydroxylase (PAH) gene in 212 unrelated patients using PCR and direct sequencing. A total of 79 different mutations were identified in 405 of 424 mutant PAH alleles including 15 novel ones. Eight mutations, R243Q, Ex6–96A>G, IVS4 − 1G>A, R413P, Y356X, R111X, R241C, and V399V, with a relative frequency of 3% or more, accounted for two thirds of the identified ones. The data presented in this study indicates that the total pool of mutant PAH alleles in China consisted of a small number of common mutations and a very high number of rare mutations. Moreover, by merging the findings of previous studies to generate a more composite data set for the Chinese mainland, it is shown that there are no significant differences of the common mutations between southern and northern except for R413P statistically, raising questions about the previous hypothesis that great variations on mutation frequencies exist between above regions.