Zeng Baitao, Lu Qing, Chen Shaohong, Guan Huizhen, Xu Xiaolan, Zou Yongyi, Wang Feng, Huang Shuhui, Liu Yanqiu, Yang Bicheng
Department of Medical Genetics, Jiangxi Maternal and Child Health Hospital, Nanchang, China.
Jiangxi Provincial Key Laboratory of Birth Defect for Prevention and Control, Jiangxi Maternal and Child Health Hospital, Nanchang, China.
Front Genet. 2023 Feb 9;14:1049816. doi: 10.3389/fgene.2023.1049816. eCollection 2023.
Phenylalanine hydroxylase deficiency (PAHD) is an autosomal recessive disorder of amino acid metabolism and caused by mutations in the phenylalanine hydroxylase () gene. Without timely and appropriate dietary management, the disturbance of amino acid metabolism may impair cognitive development and neurophysiological function. Newborn screening (NBS) can aid the early diagnosis of PAHD, which can give accurate therapy to PAHD patients in time. In China, the PAHD incidence and mutation spectrum vary enormously across the provinces. A total of 5,541,627 newborns from Jiangxi province were screened by NBS between 1997 and 2021. One seventy one newborns from Jiangxi province were diagnosed with PAHD. By Sanger sequencing and the multiplex ligation-dependent probe amplification (MLPA) analysis, mutation analysis was performed in 123 PAHD patients. Using an arbitrary values (AV)-based model, we compared the observed phenotype with the predicted phenotype based on the genotype. In this study, we speculated the PAHD incidence of Jiangxi province was about 30.9 per 1,000,000 live births (171/5,541,627). We summarized the mutation spectrum in Jiangxi province for the first time. Two novel variants (c.433G > C, c.706 + 2T > A) were found. The most prevalent variant was c.728G > A (14.1%). The overall prediction rate of the genotype-phenotype was 77.4%. This mutation spectrum is very meaningful to improve the diagnostic rate of PAHD and to increase the accuracy genetic counseling. This study offers data for the genotype-phenotype prediction suitable for Chinese population.
苯丙氨酸羟化酶缺乏症（PAHD）是一种常染色体隐性氨基酸代谢紊乱疾病，由苯丙氨酸羟化酶（PAH）基因突变引起。若不及时进行适当的饮食管理，氨基酸代谢紊乱可能会损害认知发育和神经生理功能。新生儿筛查（NBS）有助于PAHD的早期诊断，从而能及时为PAHD患者提供准确的治疗。在中国，PAHD的发病率和PAH突变谱在各省之间差异极大。1997年至2021年期间，江西省共有5541627名新生儿接受了NBS筛查。江西省有171名新生儿被诊断为PAHD。通过桑格测序和多重连接依赖探针扩增（MLPA）分析，对123例PAHD患者进行了突变分析。使用基于任意值（AV）的模型，我们将观察到的表型与基于基因型预测的表型进行了比较。在本研究中，我们推测江西省PAHD的发病率约为每100万活产30.9例（171/5541627）。我们首次总结了江西省的PAH突变谱。发现了两个新的变异（c.433G>C，c.706+2T>A）。最常见的变异是c.728G>A（14.1%）。基因型-表型的总体预测率为77.4%。这种突变谱对于提高PAHD的诊断率和增加遗传咨询的准确性非常有意义。本研究为适合中国人群的基因型-表型预测提供了数据。
