关键词: 苯丙酮尿症, 苯丙氨酸羟化酶, 遗传代谢病, 基因突变

Abstract: Objective To analyze the mutation characteristics of phenylalanine hydroxylase (PAH) gene in children with phenylketonuria (PKU) in Heze,Shandong,in order to provide scientific reference for further diagnosis and gene treatment of PKU. Methods For children with PKU who were clinically diagnosed and voluntarily underwent genetic testing,high-throughput sequencing technology was used to detect genes related to genetic metabolic diseases in patients,and the detected loci were verified by sanger sequencing and parental verification. Results A total of 53 pathogenic variants were detected in 28 children,of which 25 children were detected with 2 definite pathogenic alleles (89.3%),and 3 patients was detected with 1 variant allele gene (10.7%). Among the 53 mutation types,there were 38 missense mutations (71.7%),4 splicing mutations (7.5%) and 11 nonsense mutations (20.8%). The mutation sites were distributed in the 2^nd,3^rd,6^th,7^th,9^th-11^th and 4^th intron regions of PAH gene. There were 50 (94.3%) variation sites in the exon region and 3 (5.7%) variation sites in the intron region. In children with typical PKU,c.1068C>A was the predominant variation site. While the variation sites of children with mild PKU mainly included c.158G＞A,c.728G>A,and children with mild HPA were presented with variation sites of c.158G>A and c.1068C>A. The detection of c.158G＞A,c.728G＞A and c.1068c＞A was high. c.158G＞A was detected in children with mild PKU and mild HPA,with a mean Phe concentration of 860.74 μmol/L. And c.728G＞A was detected in children with typical PKU and mild PKU,with a mean Phe concentration of 879.51 μmol/L. c.1068C＞A was detected in children with typical PKU and mild HPA,with a mean Phe concentration of 1 098.44 μmol/L. Conclusion The main mutations of PAH gene in children with PKU in Heze include c.158G>A,c.728G>A and c.1068C>A.

Key words: phenylketonuria, phenylalanine hydroxylase, genetic metabolic disease, genetic mutations