中国当代儿科杂志2025，Vol.27Issue(7)：808-814,7.DOI:10.7499/j.issn.1008-8830.2502040
甘肃地区1159例苯丙酮尿症患儿基因型与干预策略分析
Genetic profiling and intervention strategies for phenylketonuria in Gansu,China:an analysis of 1159 cases
摘要
Abstract
Objective To investigate the molecular epidemiology of children with phenylketonuria(PKU)in Gansu,China,providing foundational data for intervention strategies.Methods A retrospective analysis was conducted on 1 159 PKU families who attended Gansu Provincial Maternity and Child Care Hospital from January 2012 to December 2024.Sanger sequencing,multiplex ligation-dependent probe amplification,whole exome sequencing,and deep intronic variant analysis were used to analyze the PAH gene.Results For the 1 159 children with PKU,2 295 variants were identified in 2 318 alleles,resulting in a detection rate of 99.01%.The detection rates were 100%(914/914)in 457 classic PKU families,99.45%(907/912)in 456 mild PKU families,and 96.34%(474/492)in 246 mild hyperphenylalaninemia families.The 2 295 variants detected comprised 208 distinct mutation types,among which c.728G>A(14.95%,343/2 295)had the highest frequency,followed by c.611A>G(4.88%,112/2 295)and c.721C>T(4.79%,110/2 295).The cumulative frequency of the top 23 hotspot variants reached 70.28%(1 613/2 295),and most variant alleles were detected in exon 7(29.19%,670/2 295).Conclusions Deep intronic variant analysis of the PAH gene can improve the genetic diagnostic rate of PKU.The development of targeted detection kits for PAH hotspot variants may enable precision screening programs and enhance preventive strategies for PKU.关键词
苯丙酮尿症/基因诊断/基因变异/深部内含子/精准筛查/儿童Key words
Phenylketonuria/Genetic diagnosis/Gene variant/Deep intronic variant analysis/Precision screening/Child引用本文复制引用
张钏,达振强,闫有圣,张培,周秉博,王兴,郑雷,李修晶,郭金仙,陈丕亮,惠玲..甘肃地区1159例苯丙酮尿症患儿基因型与干预策略分析[J].中国当代儿科杂志,2025,27(7):808-814,7.基金项目
北京市自然科学基金(7232062) （7232062）
甘肃省卫生健康行业科技创新重大科研项目(GSWSQNPY2025-19) （GSWSQNPY2025-19）
甘肃省科技计划资助项目(22YF7FA094) （22YF7FA094）
医院科研基金项目资助项目(GMCCH2024-2-2、GMCCH2025-2-3-08) （GMCCH2024-2-2、GMCCH2025-2-3-08）
甘肃省卫生行业计划项目(GSWSKY2022-33) （GSWSKY2022-33）
甘肃省科技厅创新基地及人才计划(21JR7RA680) （21JR7RA680）
甘肃省自然科学基金(1606RJZA151). （1606RJZA151）
