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

Q3 Medicine

中国当代儿科杂志 Pub Date : 2025-07-15 DOI:10.7499/j.issn.1008-8830.2502040

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

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引用次数: 0

Abstract

Objectives: 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.

查看原文本刊更多论文

[中国甘肃1 159例苯丙酮尿的基因分析及干预策略]。

目的：了解甘肃省儿童苯丙酮尿症（PKU）的分子流行病学，为制定干预策略提供基础数据。方法：对2012年1月至2024年12月在甘肃省妇幼保健院就诊的1 159个北大儿科患儿家庭进行回顾性分析。采用Sanger测序、多重连接依赖探针扩增、全外显子组测序和深度内含子变异分析分析PAH基因。结果：1 159例PKU患儿中，2 318个等位基因中检出2 295个变异，检出率为99.01%。457例典型PKU家族检出率为100%(914/914)，456例轻度PKU家族检出率为99.45%(907/912)，246例轻度高苯alaninemia家族检出率为96.34%（474/492）。检测到的2 295个变异包括208种不同的突变类型，其中c.728G>A（14.95%, 343/2 295）频率最高，其次是c.611A>G（4.88%, 112/2 295）和c.721C>T（4.79%, 110/2 295）。前23个热点变异的累积频率为70.28%(1 613/2 295)，变异等位基因最多出现在第7外显子（29.19%,670/2 295）。结论：对PAH基因进行深度内含子变异分析可提高PKU的遗传诊断率。多环芳烃热点变异的靶向检测试剂盒的开发可以实现精确筛选程序和加强PKU的预防策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

中国当代儿科杂志 Medicine-Pediatrics, Perinatology and Child Health

CiteScore

1.50

自引率

0.00%

发文量

5006

期刊介绍： The Chinese Journal of Contemporary Pediatrics (CJCP) is a peer-reviewed open access periodical in the field of pediatrics that is sponsored by the Central South University/Xiangya Hospital of Central South University and under the auspices of the Ministry of Education of China. It is cited as a source in the scientific and technological papers of Chinese journals, the Chinese Science Citation Database (CSCD), and is one of the core Chinese periodicals in the Peking University Library. CJCP has been indexed by MEDLINE/PubMed/PMC of the American National Library, American Chemical Abstracts (CA), Holland Medical Abstracts (EM), Western Pacific Region Index Medicus (WPRIM), Scopus and EBSCO. It is a monthly periodical published on the 15th of every month, and is distributed both at home and overseas. The Chinese series publication number is CN 43-1301/R；ISSN 1008-8830. The tenet of CJCP is to “reflect the latest advances and be open to the world”. The periodical reports the most recent advances in the contemporary pediatric field. The majority of the readership is pediatric doctors and researchers.