Study on mutations of gene in children with phenylalanine hydroxylase deficiency in Qingdao
DU Wei, YANG Gui-yun, LU Wei-bing,et al
1. QingdaoWomen and Children's Hospital affiliated to Qingdao University, Child Healthcare Department, Shandong,Qingdao 266000, China; 2. Maternal and Child Health Hospital of Zhangqiu, Child Healthcare Department,Shandong, Jinan 250200, China
Abstract: 【Abstract】 Objective To explore the mutation characteristics of phenylalanine hydroxylase (PAH)gene in children with PAH deficiency in Qingdao, and provide scientific reference for prenatal diagnosis and treatment. Methods Genetic analysis was performed on 44 children with PAH deficiency detected by neonatal screening in Qingdao. The second generation high-throughput sequencing and multi-ligaseprobe dependent amplification (MLPA) technique were used for gene analysis to detect the mutation sites in children, and Sanger sequencing was used to detect and verify the corresponding mutation sites of their parents. According to the concentration of phenylalanine in children's blood, PAH deficiency is divided into phenylketonuria (PKU), mild PKU and mild hyperphenylalanine (HPA). Results ① There were two mutation sites in each case. Two of the 44 children with PAH deficiency had homozygous mutations in the PAH gene and the frequency of homozygous mutations was 4.6%. All mutations were detected in their parents' corresponding mutation sites. ② A total of 36 mutations were found in 44 patients with PAH deficiency. The mutation frequency of c.728G > A was the highest (15.9%, 14/88), and that of c.1068C>A and c.158G>A was 10.2% (9/88) and 9.1% (8/88). ③ There were 19 PAH gene mutations in 21 children with PKU. The mutation frequency of c.1068C>A was the highest (21.4%, 9/42), and that of c.728G>A was 19.0% (8/42). There were 14 PAH gene mutations in 10 children with mild PKU. The mutation frequency of c.721C>T/722delG was the highest (15.0%, 3/20), and that of c.1197A>T, c.1301C>A, c.721C>T, and c .728G>A was 10.0% (2/20). There were 17 PAH gene mutations in 13 children with mild HPA. The mutation frequency of c.158G>A was the highest (26.9%,7/26), and that of c.728G>A was 15.4% (4/26). Conclusions The mutation of PAH gene in children with PAH deficiency in Qingdao is mainly heterozygous mutation and has obvious hot spot mutations (c.728G > A, c.1068C > A, c.158G > A). Children with PKU were mainly c.1068C>A, c.728G>A, while children with mild PKU were mainly c.721C>T/722delG, and children with mild HPA were mainly c.158G>A. The study of PAH gene mutations lays the foundation for the in-depth development of PAH deficiency genetic diagnosis, prenatal diagnosis and further gene therapy.
杜玮 杨桂芸 陆薇冰 张立琴 王岩艳 王博. 青岛市苯丙氨酸羟化酶缺乏症患儿基因突变分析[J]. 发育医学电子杂志, 2020, 8(1): 24-28.
DU Wei, YANG Gui-yun, LU Wei-bing, et al. Study on mutations of gene in children with phenylalanine hydroxylase deficiency in Qingdao. Journal of Developmental Medicine(Electronic Version), 2020, 8(1): 24-28.
2020, Vol. 8 
