Medical Genetic Diagnosis and Therapy Center, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350001, Fujian Province, China.
Obstetrics and Gynecology Department, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350001, Fujian Province, China.
Mol Biol Rep. 2022 Nov;49(11):10409-10419. doi: 10.1007/s11033-022-07579-8. Epub 2022 Sep 14.
Phenylalanine hydroxylase deficiency (PAHD) is the most prevalent inherited disorder of amino acid metabolism in China. Its complex phenotype includes many variants and genotypes among different populations.
In this study, we analyzed the phenylalanine hydroxylase gene (PAH) variants in a cohort of 93 PAHD patients from Fujian Province. We also assessed genotype and phenotype correlation in patients with PAHD. A total of 44 different pathogenic variants were identified, including five novel variants. The three most prevalent variants among all patents were c.158G > A, p.(Arg53His) (18.03%), c.721C > T, p.(Arg241Cys) (14.75%), and c.728G > A, p.(Arg243Gln) (7.65%). The frequency of the c.158G > A, p.(Arg53His) variant was highest in patients with mild hyperphenylalaninemia, whereas the frequency of the c.1197A > T, p.(Val399 =) and c.331C > T, p.(Arg111Ter) variants was highest in patients with classic phenylketonuria. The most abundant genotypes observed in PAHD patients were c.[158G > A];[728G > A], c.[158G > A];[442-1G > A], and c.[158G > A];[721C > T]. Comparing allelic phenotype to genotypic phenotype values yielded fairly accurate predictions of phenotype, with an overall consistency rate was 85.71% for PAHD patients.
Our study identified a PAH variant spectrum in PAHD patients from Fujian Province, Southeastern China. Quantitative correlation analysis between genotype and phenotype severity is helpful for genetic counseling and management.
苯丙氨酸羟化酶缺乏症（PAHD）是中国最常见的氨基酸代谢遗传障碍。其复杂表型在不同人群中存在多种变异和基因型。
本研究分析了来自福建省的 93 例 PAHD 患者的苯丙氨酸羟化酶基因（PAH）变异。还评估了 PAHD 患者的基因型和表型相关性。共鉴定出 44 种不同的致病性变异，包括 5 种新变异。所有患者中最常见的三个变异是 c.158G>A、p.(Arg53His)（18.03%）、c.721C>T、p.(Arg241Cys)（14.75%）和 c.728G>A、p.(Arg243Gln)（7.65%）。c.158G>A、p.(Arg53His) 变异在轻度高苯丙氨酸血症患者中的频率最高，而 c.1197A>T、p.(Val399=)和 c.331C>T、p.(Arg111Ter) 变异在经典苯丙酮尿症患者中的频率最高。PAHD 患者最常见的基因型是 c.[158G>A];[728G>A]、c.[158G>A];[442-1G>A]和 c.[158G>A];[721C>T]。将等位基因表型与基因型表型值进行比较，对表型进行了相当准确的预测，PAHD 患者的总体一致性率为 85.71%。
本研究在中国东南部福建省的 PAHD 患者中确定了 PAH 变异谱。基因型与表型严重程度的定量相关性分析有助于遗传咨询和管理。
