Journal of Clinical Pediatrics >
Screening of newborns with hyperphenylalaninemia and analysis of PAH gene mutation and deletion
Received date: 2021-11-29
Online published: 2023-02-16
Objective To understand the incidence, clinical typing, and variant characteristics of related genes in neonates with hyperphenylalaninemia (HPA) in Shijiazhuang. Methods 487,380 newborns underwent HPA screening in Shijiazhuang Disease Screening and Diagnosis Center from March 2017 to May 2021 were selected. The phenylalanine concentration in heel blood samples was detected by immunofluorescence, the phenylalanine hydroxylase (PAH) related genes of suspected positive children were detected by gene sequencing, and the target gene variants were verified by the Sanger sequencing in the parents of the children, and the results of gene sequencing were further compared with the normal people to fragment deletion regions. Results Among the 487,380 neonates, 191 were screened positive and 104 were diagnosed as HPA, all with PAH deficiency, with a prevalence of 1/4686. A total of 62 genetic variations were detected in 104 children, including 37 missense mutations, 10 splice mutations, 7 nonsense mutations, 2 synonymous mutations, 1 full code mutation and 5 heterozygous deletions. The most common variants of PAH gene are c.158G>A (18.7%), c.728G>A (10.5%), c.611A>G (6.7%), c.331C>T (4.8%) and c.721C>T (4.8%), and unreported gene fragment deletions (exon 6 heterozygous deletion) and gene variants (c.630T>G, c.61-1G>A, c.912+5G>A) were found. Conclusions The prevalence of HPA in Shijiazhuang was high at 1/4686; 62 PAH gene variants, including 5 fragment deletions, were identified; in addition, 5 unreported gene variants were found, which enriches the gene database.
Cuixia MA , Lulu Feng , Qianqian Ma , Yang Li , Jizhen Feng . Screening of newborns with hyperphenylalaninemia and analysis of PAH gene mutation and deletion[J]. Journal of Clinical Pediatrics, 2023 , 41(2) : 98 -102 . DOI: 10.12372/jcp.2023.21e1659
[1] | 中华医学会儿科学分会内分泌遗传代谢学组, 中华预防医学会出生缺陷预防与控制专业委员会新生儿筛查学组. 高苯丙氨酸血症的诊治共识[J]. 中华儿科杂志, 2014, 52(6): 420-423. |
[2] | 顾学范, 叶军. 新生儿疾病筛查[M]. 上海: 上海科学技术文献出版社, 2003: 138-166. |
[3] | 叶军, 邱文娟, 韩连书, 等. 新生儿筛查诊断的223例高苯丙氨酸血症的诊治及随访[J]. 中华预防医学杂志, 2007, 41(3): 189-192. |
[4] | Loeber JG. Neonatal screening in Europe; the situation in 2004[J]. J Inherit Metab Dis, 2007, 30(4): 430-438. |
[5] | Pangkanon S, Charoensiriwatana W, Janejai N, et al. Detection of phenylketonuria by the newborn screening program in Thailand[J]. Southeast Asian J Trop Med Public Health, 2009, 40(3): 525-529. |
[6] | 赵振东, 黄慈丹, 许海珠, 等. 海南省380 996名新生儿苯丙酮尿症筛查及苯丙氨酸羟化酶基因分析[J]. 中华医学杂志, 2020, 100(26): 2054-2058. |
[7] | 孙巧玲. 安徽省新生儿遗传代谢性疾病筛查项目效果分析[J]. 中国妇幼保健, 2019, 34(23): 5462-5464. |
[8] | 贺金峰, 苏雅洁, 阿米娜·艾买提, 等. 新疆阿克苏地区23万新生儿疾病筛查及确诊患儿的治疗随访分析[J]. 中国生育健康杂志, 2019, 30(3): 277-280. |
[9] | 马胜举, 赵德华, 马坤, 等. 河南省2013—2019年新生儿遗传代谢病筛查回顾性分析[J]. 检验医学与临床, 2020, 17(14): 1965-1968. |
[10] | 周伟, 李惠中, 杨丽, 等. 徐州地区苯丙酮尿症筛查及致病基因谱特征研究[J]. 中华新生儿科杂志, 2021, 36(2): 16-21. |
[11] | 胡海利, 李卫东, 邵子瑜, 等. 72例安徽地区高苯丙氨酸血症患儿苯丙氨酸羟化酶基因变异观察[J]. 山东医药, 2018, 58(3): 70-72. |
[12] | 张璋, 张立琴, 杜玮, 等. 苯丙氨酸羟化酶缺乏症患儿基因型和表型关系及其临床应用的研究[J]. 临床儿科杂志, 2020, 38(9): 671-678. |
[13] | 张瑞雪, 宋成荣, 张言, 等. 串联质谱联合二代测序技术在陕西地区遗传代谢病诊断中的应用[J]. 国际遗传学杂志, 2020, 43(6): 317-323. |
[14] | Okano Y, Kudo S, Nishi Y, et al. Molecular characterization of phenylketonuria and tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency in Japan[J]. J Hum Genet, 2011, 56(4): 306-312. |
[15] | Trunzo R, Santacroce R, Shen N, et al. In vitro residual activity of phenylalanine hydroxylase variants and correlation with metabolic phenotypes in PKU[J]. Gene, 2016, 594(1): 138-143. |
[16] | 张展, 刘昕, 高峻峻, 等. 83例苯丙酮尿症患者pah基因大片段缺失的检测[J]. 重庆医学, 2018, 47(34): 4374-4378. |
/
〈 |
|
〉 |