摘要目的:探讨苯丙氨酸羟化酶(PAH)缺乏症相关的 PAH基因c.158G>A变异的致病性以及与表型的相关性。 方法:回顾分析2016年7月至2021年6月南京医科大学附属妇产医院确诊的37例PAH缺乏症患儿的临床资料和基因检测结果。结果:在37例患儿中，轻度高苯丙氨酸血症(HPA)共34例，其中33例检测到2处 PAH变异(包括c.158G>A)且均为复合杂合子，1例检测到3处 PAH变异，包括c.158G>A纯合变异及c.842＋2T>A杂合变异。3人为经典型苯丙酮尿症(PKU)，并携带3处 PAH变异，在其中2例中c.158G>A与c.842＋2T>A呈顺式排列，基因型为c.[158G>A，842＋2T>A]/c.728G>A和c.[158G>A，842＋2T>A]/c.611A>G，在另1例中158G>A与c.722G>A呈顺式排列，基因型为c.[158G>A，c.722G>A]/c.728G>A。其中，c.158G>A变异对PAH的活性影响较小，与轻度HPA表型相关，可归类为"可能良性"变异，但患者的临床表型还与另一等位基因的变异类型有关。 结论:37例PAH缺乏症患儿遗传学研究提示，c.158G>A变异与其他致病变异呈顺式排列时，患者的临床表型主要取决于其余2个变异的致病性。

abstractsObjective:To explore the pathogenicity and genotype-phenotype correlation of a c. 158G>A variant of phenylalanine hydroxylase ( PAH) gene among patients with PAH deficiency. Methods:Thirty seven children diagnosed with PAH deficiency at the Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University between July 2016 and June 2021 were selected as the study subjects. Clinical data and results of genetic testing were retrospectively analyzed.Results:Among the 37 patients, mild hyperphenylalaninemia (HPA) was observed in 34 cases, two PAH variants (including c. 158G>A), which formed a compound heterozygous mutation genotype, were detected in 33 patients, and the remainder one was found to harbor three PAH variants, including homozygous c. 158G>A variants and a heterozygous c. 842+ 2T>A variant. Classical phenylketonuria (PKU) was observed in 3 patients, and three PAH variants were detected in each of them, including two with c. [158G>A, 842+ 2T>A]/c.728G>A and c. [158G>A, 842+ 2T>A]/c.611A>G, respectively, and one with c. [158G>A, c. 722G>A]/c.728G>A. The c. 158G>A variant has a minimal influence on the PAH activity and is associated with a mild HPA phenotype. The variant should thereby be classified as likely benign. Conclusion:When the c. 158G>A variant and other pathogenic variants are arranged in cis position, the ultimate phenotype will be determined by the pathogenicity of other variants.