关键词: 高苯丙氨酸血症, 发病率, 苯丙氨酸羟化酶, 基因变异, 新生儿

Abstract:

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.

Key words: hyperphenylalaninemia, incidence rate, phenylalanine hydroxylase, gene mutation, newborn