Zhao Dehua, Li Xiaole, Jia Chenlu, Ni Min, Kong Xiangdong
The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2016 Jun;33(3):300-5. doi: 10.3760/cma.j.issn.1003-9406.2016.03.005.
To delineate the mutation spectrum of phenylalanine hydroxylase (PAH) gene among patients affected with phenylalanine hydroxylase deficiency (PAHD) in Henan Province of China, and to explore the correlation between the genotype and the phenotype.
A total of 155 affected children were recruited. Potential mutation of the PAH gene were analyzed by direct sequencing. The genotype-phenotype correlation was analyzed by matching the expected and observed phenotypes.
Over 72 mutations and 108 genotypes have been identified. There were 7 homozygous mutations, including 1 case with EX6-96A>G/EX6-96A>G, 1 with R241C/R241C, 1 with R413P/R413P, and 4 with R243Q/R243Q. Among these, 6 patients have presented classic PKU phenotypes, except for a R241C/R241C genotype which has led to mild PKU. In 104 patients carrying compound PAH mutations, 52 were classic, 34 were mild and 39 had mild HPA. Patients who were heterozygous for EX6-96A>G/R241C, R243Q/A434D, EX6-96A>G/R413P and EX6-96A>G/ R241C were found with both the classic PKU and mild PKU phenotypes. Common mutations associated with mild HPA have included R53H, R243Q, V399V and H107R. The common mutations associated with mild PKU included R243Q, R241C, EX6-96A>G, and IVS4-1G>A. The prevalent mutations in classic PKU were R243Q, EX6-96A>G and V399V. The consistency between prediction of the biochemical genotype and observed phenotype was 77.78%, especially in classic PKU, the consistency was up to 82.14%. Significant correlations were disclosed between pretreatment levels of phenylalanine and AV sum (r=-0.6729, P < 0.01).
The mutation spectrum of PAH gene in Henan seems to differ from that of other regions. Independent assortment of mutant alleles may result in a complex genotype-phenotype correlation, but the genotypes of PAHD patients have correlated with the phenotype.
明确中国河南省苯丙氨酸羟化酶缺乏症（PAHD）患者中苯丙氨酸羟化酶（PAH）基因的突变谱，并探讨基因型与表型之间的相关性。
共招募了155名患病儿童。通过直接测序分析PAH基因的潜在突变。通过匹配预期和观察到的表型来分析基因型-表型相关性。
已鉴定出72种以上的突变和108种基因型。有7种纯合突变，包括1例EX6-96A>G/EX6-96A>G、1例R241C/R241C、1例R413P/R413P和4例R243Q/R243Q。其中，6例患者表现出经典苯丙酮尿症（PKU）表型，除了一种R241C/R241C基因型导致轻度PKU。在104例携带复合PAH突变的患者中，52例为经典型，34例为轻型，39例为轻度高苯丙氨酸血症（HPA）。发现EX6-96A>G/R241C、R243Q/A434D、EX6-96A>G/R413P和EX6-96A>G/R241C杂合的患者同时具有经典PKU和轻度PKU表型。与轻度HPA相关的常见突变包括R53H、R243Q、V399V和H107R。与轻度PKU相关的常见突变包括R243Q、R241C、EX6-96A>G和IVS4-1G>A。经典PKU中的常见突变是R243Q、EX6-96A>G和V399V。生化基因型预测与观察到的表型之间的一致性为77.78%，特别是在经典PKU中，一致性高达82.14%。苯丙氨酸预处理水平与AV总和之间存在显著相关性（r=-0.6729，P<0.01）。
河南PAH基因的突变谱似乎与其他地区不同。突变等位基因的独立组合可能导致复杂的基因型-表型相关性，但PAHD患者的基因型与表型相关。
