Analysis of pathogenicity and genotype-phenotype correlation of the c. 158G>A variant of phenylalanine hydroxylase gene
10.3760/cma.j.cn511374-20210623-00532
- VernacularTitle:苯丙氨酸羟化酶基因c.158G>A变异的致病性及基因型-表型相关性分析
- Author:
Peiying YANG
1
;
Yun SUN
;
Xin WANG
;
Dingyuan MA
;
Yanyun WANG
;
Zhilei ZHANG
;
Tao JIANG
Author Information
1. 南京医科大学附属妇产医院（南京市妇幼保健院）遗传医学中心，南京 210004
- Keywords:
Phenylalanine hydroxylase;
PAH gene;
c. 158G>A variant
- From:
Chinese Journal of Medical Genetics
2024;41(3):278-283
- CountryChina
- Language:Chinese
-
Abstract:
Objective: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.
