Mashhad University of Medical Sciences, Human Genetics Department, Mashhad-Iran.
Gene. 2012 Sep 10;506(1):230-2. doi: 10.1016/j.gene.2012.06.043. Epub 2012 Jul 2.
Characterization of the molecular basis of phenylketonuria (PKU) in North-east of Iran has been accomplished through the analysis of 62 unrelated chromosomes from 31 Iranian PKU patients.
Phenylalanine hydroxylase (PAH) gene mutations have been analyzed by direct DNA sequencing exons 6, 7, 10 and 11.
A mutation detection rate of 74% was achieved. Eleven different mutations were found, with the most frequent mutation, IVS10-11G>A, accounting for 19% of Khorasan-Razavi PKU alleles. Ten mutations (R176X, E280K, IVS11+1G>C, S231P, Q383X, R243X, I224T, E390G, R252W and P281L) represent the rest PKU chromosomes. One novel mutation, Q383X in the homozygote form was identified which is located in the catalytic domain (residues143-410).
With this high detection rate of mutations in North-east of Iran, new strategy for carrier testing could be DNA sequencing of these four exons. The other exons and boundaries will be studied only when either one or no mutations are detected in the initial screen.
通过对 31 名伊朗苯丙酮尿症（PKU）患者的 62 条无关染色体进行分析，已经完成了对伊朗东北部苯丙酮尿症的分子基础的特征描述。
通过直接 DNA 测序分析外显子 6、7、10 和 11，分析苯丙氨酸羟化酶（PAH）基因突变。
实现了 74%的突变检测率。发现了 11 种不同的突变，最常见的突变是 IVS10-11G>A，占霍拉桑-拉扎维 PKU 等位基因的 19%。其他 10 种突变（R176X、E280K、IVS11+1G>C、S231P、Q383X、R243X、I224T、E390G、R252W 和 P281L）代表了其余的 PKU 染色体。在纯合子形式下发现了一种新的突变 Q383X，位于催化结构域（残基 143-410）。
在伊朗东北部，这种高突变检测率表明，对于携带者的检测可以采用这四个外显子的 DNA 测序。只有在初始筛选中检测到一个或没有突变时，才会研究其他外显子和边界。
