新疆维吾尔族家系中PAH基因R111X纯合子突变研究

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）。

Studies on R111 homozygous mutation of PAH gene in Xinjiang Uigur family

Objective： To identify the gene mutation of phenylalanine hydroxylase （PAH） in Xinjiang Uigur family with phenylketonuria （PKU）, and investigate the disposition and frequency of the mutant gene. Methods： Single strand conformation polymorphism （SSCP） essay and sequence analysis of the PCR product were used to ascertain the gene mutation of phenylalanine hydroxylase （PAH）. Results： Single strand conformation polymorphism （SSCP） essay was used to screen exons 3, exons 5, exons 6, exons 7, exons 11 and exons 12 of aeger and his parents. There are differences in SSCP electrophoresis strips between the aeger and normal, also between the aeger and his parents. It was demonstrated from sequencing result that C→T mutation has happened on the site 331 of the aeger＇s PAH cDNA. Unlike their child＇s R111 homozygote mutation, the aeger＇s parents are heterozygotes, although they have the same site mutation. Conclusion： It is the first time that R111 homozygote mutation was found in minority ethnic group internal. According to the PKU ratio of Uigur group and Han group and the probability of homozygote, altofrequent R111 gene mutation should happened in Uigur group. After aggregate analysis of the disposition and the frequency of the R111 mutatant gene in both here and abroad, it is concluded that the peak of R111 mutatant gene is in North China, and it is also presumed that the north area around Tianjin is the founder of R111 mutatant gene.