Department of Prenatal Diagnosis Center, General Hospital of Ningxia Medical University, 750004 Yinchuan, Ningxia, China.
Department of Reproductive Medicine, Yinchuan Maternity and Child Health Care Hospital, 750004 Yinchuan, Ningxia, China.
Discov Med. 2023 Aug;35(177):533-538. doi: 10.24976/Discov.Med.202335177.54.
Phenylalanine hydroxylase deficiency (PAHD) is an autosomal recessive disorder affecting phenylalanine (Phe) metabolism caused by mutations in the phenylalanine hydroxylase () gene. It has a complex phenotype with many variants and genotypes in various populations. This study sets out to analyze the screening results of children with phenylketonuria (PKU) in Yinchuan City and characterize the mutation variants of the gene.
Phenylketonuria screening results were retrospectively analyzed in 398,605 neonates (207,361 males and 191,244 females) born in different maternity hospitals in Yinchuan City between January 2017 and December 2021. Screening for genetic metabolic diseases was performed with parental consent at their own expense. A comprehensive diagnosis was performed by integrating tandem mass spectrometry (MS/MS) findings with clinical presentations. High-throughput sequencing (HTS) was used to detect genetic and metabolic disease-associated genes in children with PKU who were clinically diagnosed and voluntarily tested. The identified loci were validated through Sanger sequencing and parental verification.
Among the screened newborns, 45 (11.3/100,000) PKU cases were diagnosed. In the 38 cases that underwent self-financed sequencing, 56 mutations were detected in 76 chromosomes, with an overall detection rate of 73.7%. All patients harbored mutant genes, and the 56 mutations detected identified represented 14 variants, including 8 missense mutations, 2 splicing mutations, 2 nonsense mutations, and 2 silent mutations. The mutations were primarily distributed in , , , , , , and , with the highest frequency observed in (25 [44.7%]), followed by (15 [26.7%]). The most prevalent mutations were -p.R252W (10 [17.9%]) and -p.R261Q (8 [14.3%]).
The gene mutations in children with PKU in Yinchuan City are predominantly concentrated in , , and , with the highest detection rates observed for p.R252W and p.R261Q mutations.
苯丙氨酸羟化酶缺乏症（PAHD）是一种常染色体隐性遗传疾病，影响苯丙氨酸（Phe）代谢，由苯丙氨酸羟化酶（）基因的突变引起。它在不同人群中有复杂的表型，存在多种变异体和基因型。本研究旨在分析银川市苯丙酮尿症（PKU）患儿的筛查结果，并描述基因的突变变异体。
回顾性分析 2017 年 1 月至 2021 年 12 月间在银川市不同妇产医院出生的 398605 名新生儿（男 207361 名，女 191244 名）的苯丙酮尿症筛查结果。遗传代谢性疾病的筛查是在父母知情同意并自费的情况下进行的。综合串联质谱（MS/MS）结果和临床表现进行全面诊断。对临床诊断并自愿检测的 PKU 患儿进行高通量测序（HTS）检测，以检测与遗传和代谢性疾病相关的基因。通过 Sanger 测序和父母验证对鉴定出的基因座进行验证。
在所筛查的新生儿中，诊断出 45 例（11.3/100000）PKU 病例。在 38 例自费进行测序的病例中，在 76 条染色体中检测到 56 种突变，总检出率为 73.7%。所有患者均携带突变基因，共检出 56 种突变，代表 14 种变异体，包括 8 种错义突变、2 种剪接突变、2 种无义突变和 2 种沉默突变。突变主要分布在、、、、、、和，其中检出频率最高的是（25 [44.7%]），其次是（15 [26.7%]）。最常见的突变是-p.R252W（10 [17.9%]）和-p.R261Q（8 [14.3%]）。
银川市 PKU 患儿的基因突变主要集中在、和，p.R252W 和 p.R261Q 突变的检出率最高。
