论文部分内容阅读
目的鉴定维吾尔族苯丙酮尿症(PKU)家系的苯丙氨酸羟化酶(PAH)基因突变,并讨论突变基因的分布和频率。方法采用单链构象多态性(SSCP)分析技术和PCR产物直接测序方法确定PAH基因突变类型。结果对患者及其父母PAH基因第3、5、6、7、11、12外显子分别进行了SSCP实验筛检,在外显子3中,发现患者SSCP电泳行为既与正常对照不同,又与父母双亲相异。测序结果显示,患者的PAHcDNA第331位发生了C→T突变,是R111X突变型纯合子,其父母也分别在同一位点发生了相同突变,但为R111X突变型杂合子。结论国内在少数民族中报道R111X纯合子突变尚属首次。根据新疆维吾尔族PKU患者与汉族患者的比例,以及形成纯合子的几率,估计R111X突变基因在维吾尔族群体中会有较高的发生频率。综合分析国内外R111X突变基因的分布及频次位置,本文认为R111X突变基因频率的高处在我国北方地区。并推测,以我国天津为中心的北方地区是R111X突变基因的建立者(founder)。
Objective To identify the phenylalanine hydroxylase (PAH) gene mutations in the Uygur phenylketonuria (PKU) pedigree and to discuss the distribution and frequency of the mutated genes. Methods Single strand conformation polymorphism (SSCP) analysis and direct sequencing of PCR products were used to determine the type of PAH mutations. Results The exon 3, 5, 6, 7, 11 and 12 of PAH gene of patients and their parents were screened by SSCP. In exon 3, SSCP electrophoresis was found to be different from that of normal control Parents different parents. The sequencing results showed that the mutation of C → T occurred in the 331th PAHcDNA of the patient, which was a R111X mutant homozygote. The parents also had the same mutation at the same locus but the R111X mutant heterozygote. Conclusion It is the first time to report the R111X homozygote mutation among ethnic minorities in China. According to the proportion of Uygur PKU patients and Han patients in Xinjiang, and the probability of forming homozygotes, it is estimated that the R111X mutation gene will have a higher frequency in the Uighur population. Comprehensive analysis of the distribution and frequency of R111X mutation at home and abroad, this paper suggests that R111X mutation frequency in the northern part of our country. It is also speculated that the northern part of China, with Tianjin as the center, is the founder of the R111X mutant gene.