Medical Genetic Center, Changzhi Maternal and Child Health Care Hospital, 38 Weiyuanmen Road, Changzhi, Shanxi 046000, China.
Medical Genetic Center, Changzhi Maternal and Child Health Care Hospital, 38 Weiyuanmen Road, Changzhi, Shanxi 046000, China.
Brain Dev. 2021 Feb;43(2):220-229. doi: 10.1016/j.braindev.2020.08.012. Epub 2020 Sep 4.
Phenylalanine hydroxylase deficiency (PAHD) is an autosomal recessive inborn error that affects phenylalanine (Phe) metabolism. It has a complex phenotype with many variants and genotypes among different populations. Shanxi province is a high-prevalence area of PAHD in China.
In this study, eighty-nine PAHD patients were subjected to genetic testing using Sanger sequencing, followed by multiplex ligation-dependent probe amplification analysis (MLPA). Allelic and genotypic phenotype values (APV and GPV, respectively) were used for genotype-based phenotypic prediction.
Fifty-one types of variants, including three novel forms, were identified. The predominant variant was p.R243Q (22.09%), followed by p.R53H (10.47%), p.EX6-96A > G (9.30%), p.V399V (5.23%) and p.R413P (3.49%). Notably, mild hyperphenylalaninemia (MHP) has a high prevalence in this region (up to 45.76%), and the variant p.R53H was solely observed in patients of MHP. According to the genotype-phenotype prediction, the APV/GPV system was well correlated with the metabolic phenotype of most PAHD patients.
We have systematically constructed the mutational and phenotypic spectrum of PAH in Shanxi province. Hence, this study will help to further understand the genotype-phenotype associations in PAHD patients, and it may offer more reliable genetic counseling and management.
苯丙氨酸羟化酶缺乏症（PAHD）是一种常染色体隐性遗传的先天代谢缺陷，影响苯丙氨酸（Phe）代谢。它具有复杂的表型，在不同人群中有许多变体和基因型。山西省是中国 PAHD 的高发地区。
本研究对 89 例 PAHD 患者进行 Sanger 测序基因检测，然后进行多重连接依赖性探针扩增分析（MLPA）。等位基因和基因型表型值（APV 和 GPV）用于基于基因型的表型预测。
共发现 51 种变体，包括 3 种新形式。主要变体是 p.R243Q（22.09%），其次是 p.R53H（10.47%）、p.EX6-96A>G（9.30%）、p.V399V（5.23%）和 p.R413P（3.49%）。值得注意的是，该地区轻度高苯丙氨酸血症（MHP）的患病率较高（高达 45.76%），且仅在 MHP 患者中观察到 p.R53H 变异。根据基因型-表型预测，APV/GPV 系统与大多数 PAHD 患者的代谢表型密切相关。
我们系统地构建了山西省 PAH 的突变和表型谱。因此，本研究将有助于进一步了解 PAHD 患者的基因型-表型相关性，并可能提供更可靠的遗传咨询和管理。
