Gene mutations in children with phenylalanine hydroxylase deficiency: an analysis of 45 cases in some regions of Chongqing

Abstract

Objective To explore the gene mutation frequency and characteristics of phenylalanine hydroxylase (PAH) in PAH deficiency children in some regions of Chongqing in order to provide scientific reference for the diagnosis and treatment of the disease. Methods A retrospective analysis was conducted on 45 children with PAH deficiency who were diagnosed in our hospital from January 1, 2014 to October 25, 2020. They was assigned into classic phenylketonuria (PKU), mild PKU and mild hyperphenylalaninemia (HPA). We analyzed the mutations of PAH gene by second-generation high-throughput sequencing and multiplex ligase probe dependent amplification (MLPA) technique, and the results were verified by the detection of corresponding mutation sites of their parents by Sanger sequencing. Results ① There were 2 mutation sites in 43 cases, including 40 cases of compound heterozygous mutation and 3 cases of homozygous mutation. All mutations were detected in the corresponding mutation sites of their parents. The left 2 cases had heterozygous mutations, and had only 1 mutation site. ② There were 34 types of mutations detected in 45 patients with PAH deficiency. Missense mutation was the main mutation type (52.9%). The mutation frequency of c.728G>A was the highest (15.9%, 14/88), followed by c.158G>A (11.4%, 10/ 88), c.1197A>T (9.1%, 8/88), and c.721C > T (9.1%, 8/88). The region of high frequency mutation was in exon 7, which contained 4 mutations and 26 mutations sites (29.5%). ③ There were 11 PAH gene mutations in 13 patients with classic PKU. The mutation frequency of c.728G> A (8/25, 32%) was the highest. There were 9 PAH gene mutations in 8 patients with mild PKU. The mutation frequency of c.728G>A (3/15, 20%) was the highest. There were 24 PAH gene mutations in 24 patients with mild HPA. The mutation frequency of c.158G>A (10/48, 20.8%). Conclusion The mutations in children with PAH deficiency in some regions of Chongqing are mainly compound heterozygosity. Missense mutation is the main type, with obvious hot spot mutations (c.728G>A, c.158G>A, c.721C > T and c.1197A>T).

Keywords

• hyperphenylalaninemia
• neonatal disease screening
• phenylalanine hydroxylase
• gene mutation