Mutation Spectrum of the Phenylalanine Hydroxylase Gene in Phenylketonuria Patients in Golestan Province, Iran

Koohpar, Zeinab Khazaei; Qasemiyan, Yashar; Ardakani, Hossein Haerian; Hashemi, Maryamalsadat; Kimiajou, Mahdieh; Mohammadian, S; Zaeri, Hossein

doi:10.1134/s1062359020060084

Cited by 4 publications

(3 citation statements)

References 22 publications

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“…25 Of note, p.Arg261Gln with allele frequency of 8.7% is the second most common mutation in Turkey. 28 This variant has a relatively high allele frequency in some parts of Iran such as Esfahan, 22 Mazandaran and Golestan, 34 , 35 Guilan, 36 Qazvin and Zanjan, 37 East Azerbaijan 24 and less allele frequency in northeast 27 as well as among Kurds. 38 The distribution of p.Arg261Gln as a CpG mutation is difficult to explain by ancient or recent migration which has a moderate allele frequency in several South European countries and high frequency in Middle East unconnected by known movement of peoples in the past.…”

Section: Resultsmentioning

confidence: 99%

Mutational landscape of phenylketonuria in Iran

Ajami

Soleimani

Hasanpour

et al. 2023

J Cellular Molecular Medi

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To date more than 1000 different variants in the PAH gene have been identified in patients with phenylketonuria (PKU). In Iran, several studies have been performed to investigate the genetics bases of the PKU in different parts of the country. In this study, we have analysed and present an update of the mutational landscape of the PAH gene as well as the population genetics and frequencies of detected variants for each cohort. Published articles on PKU mutations in Iran were identified through a comprehensive PubMed, Google Scholar, Web of Science (ISI), SCOPUS, Elsevier, Wiley Online Library and SID literature search using the terms: “phenylketonuria”, “hyperphenylalaninemia”, and “PKU” in combination with “Iran”, “Iranian population”, “mutation analysis”, and “Molecular genetics”. Among the literature‐related to genetics of PKU, 18 studies were on the PKU mutations. According to these studies, in different populations of Iran 1497 patients were included for mutation detection that resulted in detection of 129 different mutations. Results of genetic analysis of the different cohorts of Iranian PKU patients show that the most prevalent mutation in Iran is the pathogenic splice variant c.1066‐11G > A, occurring in 19.54% of alleles in the cohort. Four other common mutations were p.Arg261Gln, p.Pro281Leu, c.168 + 5G > C and p.Arg243Ter (8.18%, 6.45%, 5.88% and 3.7%, respectively). One notable feature of the studied populations is its high rate of consanguineous marriages. Considering this feature, determining the prevalent PKU mutations could be advantageous for designing screening and diagnostic panels in Iran.

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Section: Resultsmentioning

confidence: 99%

Mutational landscape of phenylketonuria in Iran

Ajami

Soleimani

Hasanpour

et al. 2023

J Cellular Molecular Medi

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“…Early diagnosis and treatment are essential to prevent PKU because the most detrimental outcome of PKU is mental retardation. Therefore, screening programs can be useful tools for the timely treatment and prevention of PKU in patients in different geographical regions of a country (5). PAH gene is 90 kb in length with 13 exons which is located on chromosome 12q22-q24.1 and encodes 452 amino acids.…”

Section: Introductionmentioning

confidence: 99%

“…The main cause of PKU is mutations in PAH gene (6), and more than 1 180 bi-allelic variants have been detected in this gene (7). The frequency of these mutations varies in different geographical regions; as a result, the identification of common mutations in each region is necessary to facilitate genetic screening (5). IVS4+1G>A (c.441+1G>A) is a splicing mutation in the intron 4 of the PAH gene.…”

Section: Introductionmentioning

confidence: 99%

Detection of IVS4+1G>A mutation in phenylalanine hydroxylase gene in North of Iran using PCR-sequencing

Chelak

Koohpar

2023

J Shahrekord Univ Med Sci

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Background and aims: Phenylketonuria (PKU) is an autosomal recessive disorder of phenylalanine (Phe) metabolism. Mutations in the phenylalanine hydroxylase (PAH) gene are the main reason for the incidence of PKU. To date, more than 1180 variants have been detected in the PAH gene. Given that the distribution pattern of mutations in the PAH gene is specific to each population, the present study was conducted to detect exon 4 mutations and adjacent flanking regions of the PAH gene in northern Iran. Methods: This is a descriptive cross-sectional study, in which 24 unrelated PKU patients in Taleghani Hospital in Gorgan were enrolled for a one-year period. After extraction of genomic DNA from leukocytes, identification of exon 4 mutations and adjacent flanking regions was performed using polymerase chain reaction (PCR) and sequencing techniques. Results: In this study, IVS4+1G>A mutation was detected in one allele (2.08%) among 48 alleles. Moreover, IVS4+47C>T and IVS3-22C>T polymorphisms were observed in 12 alleles (25%) and eight alleles (16.7%), respectively. Conclusion: In the present study, IVS4+1G>A mutation was only found in 2% of chromosomes. Hence, different mutations are responsible for PKU disease in the north of Iran, and further studies are recommended to identify all mutations in the PAH gene in the region.

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