苯丙氨酸羟化酶基因突变检测对苯丙酮尿症的诊断意义

韩宗兰; 王兰英; 王海楠

doi:10.13898/j.cnki.issn.1000-2200.2021.10.023

苯丙氨酸羟化酶基因突变检测对苯丙酮尿症的诊断意义

The significance of the phenylalanine hydroxylase gene mutation in the diagnosis of phenylketonuria

摘要

摘要:
目的探讨苯丙氨酸（PA）羟化酶（PAH）基因突变检测对苯丙酮尿症（PKU）的诊断意义及其对PKU患儿的影响。
方法选取PKU患儿135例进行临床实验，所有受试者PAH基因突变情况均采用聚合酶链式反应技术进行扩增，采用Sanger测序方法检测其突变点，PAH基因是否存在大片缺失重复采用多重连接探针扩增技术（MLPA）检测，最后将各项检测数据纳入SPSS 21.0软件处理，分析PAH突变情况及比较其PAH突变对KPU患儿智商的影响。
结果135例PKU患儿（270对PAH等位基因）中，共12例患儿有PAH基因突变，占比8.89%，突变位点共12个，其中R243Q、Y204C、R241C、IVS4-1、R413P、R111X、R261Q、W326X及Y356X等均有突变频率，各占总PAH等位基因的5.19%、5.19%、3.70%、2.96%、2.22%、1.48%和1.48%、0.74%、0.74%，而E56D、F161S、A345T等的突变频率则不明显。经SNaPShot、Sanger及MLPA检测12例PKU患儿的PAH基因突变情况发现，纯合突变占比16.67%，复合、杂合突变占比83.33%。12例PKU患儿干预后的PA低于干预前、全智商评分高于干预前，差异均具有统计学意义（P < 0.05），而言语智商、操作智商干预前后差异均无统计学意义（P>0.05）。经Pearson分析发现12例PAH基因突变的PKU患儿治疗期的PHE平均控制浓度与1周岁时的IQ检测值呈负相关（r=-0.924，P < 0.01）。
结论在PKU患儿的临床治疗过程中科学、合理地进行PAH基因突变检测并严格控制患儿的PHE血浓度有较好的临床应用与推广价值，也是改善患儿智商的关键因素之一。

Abstract:
ObjectiveTo explore the diagnostic significance of phenylalanine hydroxylase(PAH) gene mmutation in phenylketonuria(PKU), and its influence on children with PKU.
MethodsOne hundred and thirty-five children with PKU were investigated.The mutations of PAH gene in all cases were detected using polymerase chain reaction and Sanger sequencing.The large number of deletion and duplication of PAH gene were investigated using multiplex ligation-dependent probe amplification(MLPA), and the data of detection was treated with SPSS 21.0 software to analyze the mutation of PAH and its effects on intelligence quotient of KPU children.
ResultsAmong the 135 PKU children(270 pairs of PAH alleles), the PAH gene mutations in 12 children(accounted for 8.89%) were found, and 12 mutation sites were identified, the mutation frequency of R243Q, Y204C, R241C, IVS4-1, R413P, R111X, R261Q, W326X and Y356X were 5.19%, 5.19%, 3.70%, 2.96%, 2.22%, 1.48%, 1.48%, 0.74% and 0.74% of the total PAH alleles, respectively, while the mutation frequency of E56D, F161S and A345T was not obvious.The results of PAH gene mutations detected by SNaPShot, Sanger and MLPA in 12 children with PKU showed that the homozygous mutations accounted for 16.67%, and the compound and heterozygous mutations accounted for 83.33%.The PA and FIQ scores in 12 children with PKU after intervention were lower and higher than those before intervention, respectively(P < 0.05), and the differences of the VIQ and PIQ between before and after intervention were not statistically significant(P>0.05).The results of Pearson analysis showed that the mean controlled concentration of PAH in 12 PAH-mutated PKU children during treatment was negatively correlated with the intelligence quotient test value at the first year of life(r=-0.924, P < 0.01).
ConclusionsIn the process of clinical treatment of PKU children, the scientific and reasonable detection of PAH gene mutation and strict control of children's PAH blood concentration have better clinical application and promotion value, and it is also one of the key factors to improve children's intelligence quotient.

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