Genetic profiling and intervention strategies for phenylketonuria in Gansu, China: an analysis of 1 159 cases

Chuan ZHANG; Pei ZHANG; Bing-Bo ZHOU; Xing WANG; Lei ZHENG; Xiu-Jing LI; Jin-Xian GUO; Pi-Liang CHEN; Ling HUI; Zhen-Qiang DA; You-Sheng YAN

doi:10.7499/j.issn.1008-8830.2502040

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Chinese Journal of Contemporary Pediatrics ›› 2025, Vol. 27 ›› Issue (7) : 808-814. DOI: 10.7499/j.issn.1008-8830.2502040

CLINICAL RESEARCH

Genetic profiling and intervention strategies for phenylketonuria in Gansu, China: an analysis of 1 159 cases

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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.

Key words

Phenylketonuria / Genetic diagnosis / Gene variant / Deep intronic variant analysis / Precision screening / Child

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Chuan ZHANG , Pei ZHANG , Bing-Bo ZHOU , et al . Genetic profiling and intervention strategies for phenylketonuria in Gansu, China: an analysis of 1 159 cases[J]. Chinese Journal of Contemporary Pediatrics. 2025, 27(7): 808-814 https://doi.org/10.7499/j.issn.1008-8830.2502040

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