Mutations of the Phenylalanine Hydroxylase Gene in Iranian Azeri Turkish Patients with Phenylketonuria

Bonyadi, Mortaza; Omrani, Omid; Moghanjoghi, Shiva Mohamadi; Shiva, Siyamak

doi:10.1089/gtmb.2009.0153

Cited by 20 publications

(20 citation statements)

References 9 publications

(9 reference statements)

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“…This was also found to be true in our cohort, although other notable types of mutations were detected. The c.1066-11G > A splicing mutation was the most common mutation in this cohort, consistent with the high prevalence reported in several other populations, including in Iran (Bonyadi et al 2010;Zare-Karizi et al 2011;Hamzehloei et al 2012;Ajami et al 2013). The prevalence of certain other mutations in this cohort was considerably different from the prevalence reported in previous studies and in other populations.…”

Section: Mutation Detection and Landscape Of Pah Mutations In This Cosupporting

confidence: 80%

Molecular genetics of a cohort of 635 cases of phenylketonuria in a consanguineous population

Shirzadeh¹,

Saeidian

Bagherian³

et al. 2018

J of Inher Metab Disea

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Phenylketonuria (PKU) is an inborn error of amino acid metabolism caused by mutations in the phenylalanine hydroxylase (PAH) gene, characterized by intellectual deficit and neuropsychiatric complications in untreated patients with estimated frequency of about one in 10,000 to 15,000 live births. PAH deficiency can be detected by neonatal screening in nearly all cases with hyperphenylalaninemia on a heel prick blood spot. Molecular testing of the PAH gene can then be performed in affected family members. Herein, we report molecular study of 635 patients genetically diagnosed with PKU from all ethnicities in Iran. The disease-causing mutations were found in 611 (96.22%) of cases. To the best of our knowledge, this is the most comprehensive molecular genetics study of PKU in Iran, identifying 100 distinct mutations in the PAH gene, including 15 previously unreported mutations. Interestingly, we found unique cases of PKU with uniparental disomy, germline mosaicism, and coinheritance with another Mendelian single-gene disorder that provides new insights for improving the genetic counseling, prenatal diagnosis (PND), and/or pre-implantation genetic diagnosis (PGD) for the inborn error of metabolism group of disorders.

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Section: Mutation Detection and Landscape Of Pah Mutations In This Cosupporting

confidence: 80%

Molecular genetics of a cohort of 635 cases of phenylketonuria in a consanguineous population

Shirzadeh¹,

Saeidian

Bagherian³

et al. 2018

J of Inher Metab Disea

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show abstract

“…Organism/amino acid residue 372 373 374 375 376 377 378 To date, more than 30 different mutations have been detected in patients with PKU living in Iran (Bonyadi et al, 2010;Zare-Karizi et al, 2011). This study is the first to report five other mutations, Y356X, S231P, I224T, IVS11-2A>G, and V388M, in an Iranian population.…”

Section: Discussionmentioning

confidence: 79%

“…This mutation has been identified as the most common mutation in Mediterranean populations such as Turkey (Dobrowolski et al, 2011), Italy (Daniele et al, N. Ajami et al 2007), Spain (Desviat et al, 1999), Egypt (Effat et al, 1999), and Israel (Bercovich et al, 2008). In previous studies that have been performed in Iran, IVS10-11G>A was also identified with the highest frequency (Bonyadi et al, 2010;Zare-Karizi et al, 2011).…”

Section: Discussionmentioning

confidence: 93%

A preliminary mutation analysis of phenylketonuria in southwest Iran

Ajami¹,

Nezhad²,

Foroughmand³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. Phenylketonuria (PKU) is a heterogeneous and autosomal recessive metabolic disorder that is mainly caused by mutations in the hepatic phenylalanine hydroxylase (PAH) gene. This study was designed to identify PAH mutations within exons 6, 7, and 10-12 in PKU patients from southwest Iran. Forty Iranian patients with clinical and biochemically confirmed PKU were enrolled. The exons were sequenced directly and 13 different mutations were identified including I224T, S231P, R176X, c.592_613del22, R243X, R252W, R261Q, Y356X, V388M, IVS10-11G>A, IVS11+1G>C, IVS11-2A>G, and Q375R, which were associated with 23 genotypes. A novel sequence variant, Q375R (c.1124A>G), was detected in exon 11. In one patient, a typical genotype with more than two mutations (R243X/S231P/ S231P) was found. Seven different polymorphisms and three new variants were also detected in intron regions of PAH. A high mutation spectrum was predicted in the southwestern region of Iran due to its ethnic heterogeneity, especially the Khuzestan Province. The detection PAH mutations in southwest Iran of 13 different mutations, corresponding to a mutation detection rate of 53.75%, confirmed this phenomenon.

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“…R261X, the most common mutation in our study, is also detected in Iran[1011] and some countries such as Croatia,[2] Italy,[13] Brazil,[14] Germany,[2] Korea,[15] Lithuania[16] and Portugal[17] [Table 5]. This mutation as well as R176X and R243X are nonsense mutations that lead to a premature step in translation.…”

Section: Discussionmentioning

confidence: 59%

“…The frequencies of these mutations in Iranian population is <2%. [11] Furthermore, there is no report of detection of these two mutations in Isfahan[9] and Azeri Turkish (northwestern of Iran)[10] populations [Table 5]. …”

Section: Discussionmentioning

confidence: 99%

Molecular analysis of exons 6 and 7 of phenylalanine hydroxylase gene mutations in Phenylketonuria patients in Western Iran

et al. 2012

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BACKGROUND:Phenylketonuria (PKU) is an inborn error of amino acid metabolism that results from a deficiency of phenylalanine hydroxylase (PAH). According to PAH database, exons 6 and 7 and their flanking introns of PAH gene contain the greatest number of mutant alleles. Therefore, as a preliminary study, nucleotide sequence analysis of exons 6 and 7 of the PAH gene has been performed in 25 PKU patients whose ancestors lived in Kermanshah province of Iran. To date, there has been no mutation data describing the genotypes of the PKU disease in this Kurdish ethnic region background.MATERIALS AND METHODS:Twenty-five patients (aged between 2 and 23 years) participated in this study. The DNA fragments containing two exons of the PAH gene [6 and 7] and their exon-flanking intronic sequences were amplified and sequenced.RESULTS:The total of detected mutations were R261X (8%), R176X (4%), R243Q (4%), R243X (2%) and R261Q (2%), as they accounted for 20% of all mutant alleles in this study. The identified polymorphisms are: IVS5 -54 G > A (22%), Q232Q (8%) and V245V (4%). All of the detected mutations in this study are related to CpG dinucleotides in the PAH gene sequence.CONCLUSION:The frequency of R261X, the most common mutation in our study, in Iranian population is <5%. Furthermore, there is no report of detection of R176X and R243Q in Isfahan and Azeri Turkish populations. These findings confirm the common Mediterranean mutations in this local population, although with more or lower frequencies than those reported in other related studies in Iran. Therefore, it may be necessary to study the PAH gene mutations in other provinces of Iran separately.

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Mutations of the Phenylalanine Hydroxylase Gene in Iranian Azeri Turkish Patients with Phenylketonuria

Cited by 20 publications

References 9 publications

Molecular genetics of a cohort of 635 cases of phenylketonuria in a consanguineous population

Molecular genetics of a cohort of 635 cases of phenylketonuria in a consanguineous population

A preliminary mutation analysis of phenylketonuria in southwest Iran

Molecular analysis of exons 6 and 7 of phenylalanine hydroxylase gene mutations in Phenylketonuria patients in Western Iran

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