Jalali Hossein, Zamanfar Daniel, Amirzadegan Muhammad, Ghadami Farshide, Mahdavi Mahan, Mahdavi Mohammad Reza
Thalassemia Research Center, Hemoglobinopathies Institute, Mazandaran University of Medical Sciences, Sari, Iran.
Diabetes Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
Int J Prev Med. 2024 Jul 17;15:22. doi: 10.4103/ijpvm.ijpvm_50_23. eCollection 2024.
There are more than 1100 different pathogenic variants in the phenylalanine hydroxylase () gene that are responsible for phenylketonuria (PKU) diseases, and the spectrum of these mutations varies in different ethnic groups. The aim of the present study was to identify the frequency of pathogenic variants in all 13 exons of the gene among patients with PKU in Mazandaran and Golestan provinces in the north of Iran.
Forty unrelated PKU patients from Mazandaran and Golestan provinces were enrolled in the study. Genomic DNA was extracted from leukocytes using a Qiagen DNA extraction kit and polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP), and Sanger sequencing methods were applied to detect the variants. In the case of new variants, the InterVar online tool (PMID: 28132688) was used to classify the variants.
Twenty-one different pathogenic variants were observed among the 40 investigated patients. The c.106611G>A variant had the highest frequency (27.5%) in the region, and the c.168+5G>C, c.473G>A, and c.782 G>A variants were the other most frequent mutations with allelic frequencies of 7.5, 5, and 5%, respectively. Three novel pathogenic variants including c.773T>G, c.878 T>C, and c. 1245del variants were observed among the investigated patients.
The introduction of pathogenic variants in the gene in each ethnic group provides valuable data regarding the understanding of the pathogenesis of the disease and can be helpful for prenatal diagnosis programs.
苯丙氨酸羟化酶（PAH）基因中有1100多种不同的致病变异，这些变异导致苯丙酮尿症（PKU），且这些突变谱在不同种族群体中有所不同。本研究的目的是确定伊朗北部马赞德兰省和戈勒斯坦省PKU患者中PAH基因全部13个外显子的致病变异频率。
本研究纳入了40名来自马赞德兰省和戈勒斯坦省的无亲缘关系的PKU患者。使用Qiagen DNA提取试剂盒从白细胞中提取基因组DNA，并应用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）和桑格测序方法检测变异。对于新发现的变异，使用InterVar在线工具（PMID：28132688）对变异进行分类。
在40名被调查患者中观察到21种不同的致病变异。c.106611G>A变异在该地区的频率最高（27.5%），c.168+5G>C、c.473G>A和c.782 G>A变异是其他最常见的突变，等位基因频率分别为7.5%、5%和5%。在被调查患者中观察到3种新的致病变异，包括c.773T>G、c.878 T>C和c. 1245del变异。
每个种族群体中PAH基因致病变异的介绍为了解该疾病的发病机制提供了有价值的数据，并且有助于产前诊断项目。
