Volume 33, Issue 1 (April 2022)                   Studies in Medical Sciences 2022, 33(1): 54-61 | Back to browse issues page


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Khazaei Koohpar Z, Eskandarpour Z, Kamran S A, Beheshti Dafchahi H, Seyfizadeh Sarabestani S, Ranji N et al . INVESTIGATION OF THE CORRELATION BETWEEN VNTR AND PAH GENE MUTATIONS IN PKU PATIENTS IN GUILAN PROVINCE, IRAN. Studies in Medical Sciences 2022; 33 (1) :54-61
URL: http://umj.umsu.ac.ir/article-1-5763-en.html
Assistant Professor of Molecular Genetics, Faculty of Basic Sciences, Rasht Branch, Islamic Azad University, Rasht, Iran (Corresponding Author) , najmehranji@gmail.com
Abstract:   (1310 Views)
Background & Aims: VNTR alleles in the phenylalanine hydroxylase (PAH) gene are used for carrier detection and prenatal diagnosis in phenylketonuria families. The aim of this study was to investigate linkage between VNTR alleles and the PAH gene mutations in PKU patients in Guilan province, Iran.
Materials & Methods: In this descriptive cross-sectional study, 19 unrelated PKU patients from 17 Shahrivar children hospital in Rasht were enrolled. Genomic DNA was extracted from blood samples of PKU patients. Amplification of gene fragments was carried out by PCR method and underwent direct sequencing.
Results: Our analysis showed that PKU patients in Guilan province had VNTR3/VNTR3, VNTR3/VNTR7, ND/VNTR7, VNTR7/VNTR7, and VNTR8/VNTR8 genotypes in PAH gene. The frequencies of VNTR3, VNTR7, and VNTR8 alleles were 21.05%, 28.94%, and 47.4%, respectively. Length of one allele was not determined (ND) by frequency 0.03%. The linkage between was observed in some mutations of PAH gene such as R400K, R261X, R261Q, IVS4+5G>T و and IVS10-11G>A with VNTR allelels PKU patients.
Conclusion: VNTR3, VNTR7, and VNTR8 alleles can be considered as useful marker in determining PKU carriers in Guilan. Furthermore, Genetic heterogeneity and geographic variation may be the cause of correlation of different mutations with VNTR alleles in PAH gene in Guilan province.
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Type of Study: Research | Subject: ژنتیک

References
1. Parivar K, Seifati SM, Koochmeshgi J, hashemi m. Studying the level of informativity of VNTR marker on PAH gene for carrier detection of the patients with phenylketonuria in Yazd province, Iran. Med Sci J 2011;21(3):196-200. [Google Scholar]
2. Alibakhshi R, Moradi K, Ghadiri K. The status of PAH gene-VNTR alleles and mini-haplotypes associations with PAH gene mutations in Iranian Kurdish PKU patients. Med J Islam Repub Iran 2019;33:88. [DOI:10.47176/mjiri.33.88] [PMID] [PMCID]
3. Blau N. Genetics of Phenylketonuria: Then and Now. Hum. Mutat 2016;37(6):508-15. [DOI:10.1002/humu.22980] [PMID]
4. Pampukha V, Nechyporenko M, Livshyts L. Analysis of EX5del4232ins268 and EX5del955 PAH gene mutations in Ukrainian patients with phenylketonuria. Genet Dis 2017;4(2):108-10. [DOI:10.1016/j.gendis.2016.11.004] [PMID] [PMCID]
5. Gundorova P, Zinchenko RA, Makaov AK, Polyakov AV. The spectrum of mutations in the PAH gene in patients with hyperphenylalaninemia from the Karachay-Cherkess Republic. Russ J Genet 2017;53(7):813-9. [DOI:10.1134/S1022795417070043]
6. Zhou Y-A, Ma Y-X, Zhang Q-B, Gao W-H, Liu J-P, Yang J-P, et al. Mutations of the phenylalanine hydroxylase gene in patients with phenylketonuria in Shanxi, China. Genet Mol Biol 2012;35(4):709-13. [DOI:10.1590/S1415-47572012005000069] [PMID] [PMCID]
7. Abbaskhanian A, Zamanfar D, Afshar P, Asadpoor E, Rouhanizadeh H, Jafarnia A, et al. Incidence of Neonatal Hyperphenylalaninemia Based on High-performance Liquid Chromatography Confirmatory Technique in Mazandaran Province, Northern Iran (2007-2015). Int J Prev Med 2017;8:93. [PMCID]
8. Motamedi N, Godarzi E, Rahimi Pordanjani S, Valizadeh R, Moradi Y, Sohrabivafa M, et al. Incidence of Phenylketonuria in Lorestan Province, West of Iran (2006- 2016). Int J Pediatr 2017;5(4):4713-21. [Google Scholar]
9. Moradi K, Alibakhshi R, Khatami S. The proportion of tetrahydrobiopterin deficiency and PAH gene deficiency variants among cases with hyperphenyalaninemia in Western Iran. Indian J Hum Genet 2013;19(4):454-8. [DOI:10.4103/0971-6866.124375] [PMID] [PMCID]
10. Pey AL, Stricher F, Serrano L, Martinez A. Predicted effects of missense mutations on native-state stability account for phenotypic outcome in phenylketonuria, a paradigm of misfolding diseases. Am J Hum Genet 2007;81(5):1006-24. [DOI:10.1086/521879] [PMID] [PMCID]
11. Bonyadi M, Omrani O, Moghanjoghi SM, Shiva S. Mutations of the phenylalanine hydroxylase gene in Iranian Azeri Turkish patients with phenylketonuria. Genet Test Mol Biomarkers 2010;14(2):233-5. [DOI:10.1089/gtmb.2009.0153] [PMID]
12. Bagheri M, Rad IA, Jazani NH, Zarrin R, Ghazavi A. Association Between PAH Mutations and VNTR Alleles in the West Azerbaijani PKU Patients. Maedica 2014;9(3):242-7. [PMCID]
13. Williams RA, Mamotte CD, Burnett JR. Phenylketonuria: an inborn error of phenylalanine metabolism. Clin Biochem Rev 2008;29(1):31-41. [PMCID]
14. Nemati H, Yousefi SSK, Pourvatan N, Aparviz R, Farzaneh P, Koohpar ZK, et al. Mutation analysis of phenylketonuria in the North of Iran. Gene Reports 2021;24:101196. [DOI:10.1016/j.genrep.2021.101196]
15. Bagheri M, Rad IA, Jazani NH, Zarrin R, Ghazavi A. Frequency of the VNTR-Polymorphisms at the PAH Gene in the Iranian Azeri Turkish Patients with Phenylketonuria. Maedica 2015;10(4):310-4. [PMCID]
16. Abedini G, Khazaei-Koohpar Z. Identifying Variable Number of Tandem Repeat Alleles in Phenylalanine Hydroxylase Gene in Patients with Phenylketonuria in Golestan Province, Iran. J Adv Med Biomed Res 2020;28(129):198-203. [DOI:10.30699/jambs.28.129.198]
17. Saadat M, Kamkar M, Mohabatkar H, Saadat I. High Frequency of IVS10nt546 Linked to VNTR8 in Iranian PKU Patients from Fars Province. Iran Biomed J 2003;7(3):145. [Google Scholar]

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