苯丙酮尿症杂合子高危人群基因型与生化表型相关性

目的:用分子生物学方法对可疑PKU/HPA杂合子进行PAH突变基因分析,以验证生化筛查PKU/HPA杂合子方法的可行性。方法:利用PCR、SSCP和DNA测序等方法对152例已知PKU/HPA杂合子(阳性组)和29例可疑PKU/HPA杂合子(可疑组)的PAH基因部分外显子进行分析。并与健康体检者对照(对照组)结果:152例已知PKU/HPA杂合子中发现26种基因突变,突变检出率为80.9%(123/152)。29例可疑“PKU/HPA杂合子”发现5例突变,检出率为17.2%(5/29)。对照组与可疑PKU/HPA杂合子组间差异有统计学意义(P<0.05)。结论:生化方法与分子生物学方法有一定相关性,提示生化筛查法用作PKU杂合子的初筛是可行的。

Genotype and Phenotype Study in the Population of High Risk Phenylketonuria Heterozygotes

Objective: To analyze mutations of the phenylalanine hydroxylase(PAH) gene in suspect phenylketonuria (PKU) or high phenylalanine (HPA) heterozygotes by using molecular method, and compared with biochemical screening method. Methods: The exons of 3, 5, 6, 7, 10, 11 and 12 of PAH gene were analyzed with polymerase chain reaction (PCR), single strand conformation polymorphism (SSCP) and direct sequencing techniques in 152 known-PKU/HPA heterozygotes and indentified from 29 suspect PKU/HPA heterozygotes. Results: Twenty-six kinds of mutations were identified from 152 know-PKU/HPA heterozygotes. The total detectable rate was 80.9%. Five mutations were identified from 29 suspect PKU/HPA heterozygoes. The detectable rate was 17.2%. There was a significantly difference between control groud and suspect PKU/HPA heterozygotes group. Conclusion: The biochemical method is feasible for screening the suspect PKU/HPA heterozygoes as a basic test, although it does not reach an ideal concordance between the biochemical and molecular method.