Volume 26, Issue 1 (4-2019)                   RJMS 2019, 26(1): 32-39 | Back to browse issues page

XML Persian Abstract Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Madadi N, Khazaei -Koohpar Z, Ranji N. Molecular analysis of exon 6 mutations of phenylalanine hydroxylase gene in phenylketonuria patients from Guilan Province . RJMS 2019; 26 (1) :32-39
URL: http://rjms.iums.ac.ir/article-1-5294-en.html
Tonekabon Branch, Islamic Azad University, Tonekabon, Iran , khazaei@toniau.ac.ir
Abstract:   (3400 Views)
Background: Phenylketonuria (PKU) is a metabolic disorder caused by mutations in the phenylalanine hydroxylase (PAH) gene. After thalassemia, PKU is considered as the most common autosomal recessive disease in the Iranian population. Therefore, it is necessary to identify the disease-causing mutations in this population. According to the PAH database, one of the exons with the greatest number of mutant alleles is exon 6 and the surrounding introns. Accordingly, this study was designed to identify exon 6 mutations of PAH gene among PKU patients in Guilan province and compare them with studies conducted in other regions of Iran.
Methods: In this descriptive cross-sectional study, 25 PKU patients and non-relatives (1 to 21 years old) from different regions of Guilan province were identified during a one-year period. After genomic DNA extraction, mutation detection was performed by polymerase chain reaction-sequencing method.
Results: The mutations and polymorphisms identified in this study included R176X (4%) and Q232Q (46%), respectively. The patient had mHPA phenotype and her parents were 3th degree relatives.
Conclusion: Considering that the R176X mutation was only found in 4% of chromosomes in this study, achieving a complete spectrum of PAH gene mutations in PKU patients in Guilan province requires the analysis of 12 other exons. In addition, considering the difference of PAH mutation spectrum in different regions of Iran, comprehensive studies in different regions of Iran can identify specific mutations in each region and these studies can be used to advance the future preventive and therapeutic goals.
Full-Text [PDF 978 kb]   (1429 Downloads)    
Type of Study: Research | Subject: Genetic

2. 1. Fazeli Z, Vallian S. Phenylketonuria from genetics to clinics: An Iranian prospect. Iran J Biotech; 2011. 9(3): 163-172.
3. 2. Bik-Multanowski M, Kaluzny L, Mozrzymas R, Oltarzews M, Starostecka E, Lange A, et al. Molecular genetics of PKU in Poland and potential impact of mutations on BH4 responsiveness. Acta Biochim Pol; 2013. 60(4): 613-6.
4. 3. Biglari A, Saffari F , Rashvand Z, Alizadeh S, Najafipour R, Sahmani M, et al. Mutations of the phenylalanine hydroxylase gene in Iranian patients with phenylketonuria. Springer Plus; 2015. 4(1): 542.
5. 4. Zhou Y, Ma YX, Zhang QB, Gao WH, Liu JP,Yang JP, et al . Mutations of the phenylalanine hydroxylase gene in patients with phenylketonuria in Shanxi, China. Genet Mol Biol; 2012. 35(4): 709-713
6. 5. Silao CLT, Canson DM, Hernandez KN, Chiong MAD, Estrada SC, Padilla CD. Mutations of the phenylalanine hydroxylase (PAH) gene in Filipino patients with phenylketonuria. Acta Meda Philip; 2009. 43(2): 36-39
7. 6. Bagheri M, Abdi Rad I, Hosseini-jazani N, Zarrin R, Ghazavi A. Association between PAH mutations and VNTR alleles in the West Azerbaijani PKU patients. J Clin Med; 2014. 9(3): 242-247
8. 7. Zare-Karizi S, Hossini –Mazinani SM, Khazaei-koohpar Z, Seifati SM, Shahsavan-behboodi B, Akbari MT, et al. Mutation spectrum of phenylketonuria in Iranian population. Mol Genet Metab; 2011. 102(1): 29-32.
9. 8. Hanely W.Non- pku mild hyperphenylalaninemia ( MHP) – the dilemma .Molecular Genetics and Metabolism; 2011.104:23-26.
10. 9. Khemir S, Asmi ME, Sanhaji H, Feki M, Jemaa R, Tebib N, et al. Phenylketonuria is still a major cause of mental retardation in tunisia despite the possibility of treatment. Clin Neurol Neurosurg; 2011. 113:727-730
11. 10. DiLella AG, Kwok SC, ledley FD, Marvit J, Woo SL. Molecular structure and polymorphic map of the human phenylalanine hydroxylase gene. Biochemistry; 1986. 25(4): 743-749.
12. 11. Scriver CR, Waters P J, Sarkissian C, Ryan S, Prevost L, Côté D, et al. PAHdb: a locus-specific knowledgebase. Hum Mutat; 2000. 15,99-104
13. 12. Ajami N, Kazeminezhad SR, Foroughmand AM, Hasanpour M, Aminzadeh MA. A preliminary mutation analysis of phenylketonuria in southwest Iran. Genet Mol Res; 2013. 12(4) 4958-66.
14. 13. Haerian Ardakani H, Khazaei Koohpar Z, Mohammadian S. Mutations Analysis of exon 10 - 11 of phenylalanine Hydroxylase gene in phenylketonuria patients from Golestan province.
15. Razi J Med Sci; 2018. 25(172):39-46.
16. 14. Moradi K, Alibakhshi R, Ghadiri K, Khatami SR, Galehdari H. Molecular analysis of exons 6 and 7 of phenylalanine hydroxylase gene mutations in Phenylketonuria patients in Western Iran. Ind j Hum Genet; 2012. 18(3): 290
17. 15. Pourvatan N, Khazaei –Koohpar Z. Investigation of Exon 4 mutations in Phenylalanine Hydroxylase gene in Phenylketonuria patients from Guilan province using PCR-Sequencing. Feyz J Kashan Uni Med Sci; 2018. 22(6):595-601.
18. 16. Moradi K, Alibakhshi R, Alimadadi K. The frequency of the most common Mediterranean mutation in phenylketonuria patients in Kermanshah Province. Sci J Kurdistan Uni Med Sci; 2014. 19 (1):58-66
19. 17. Lee DH, Koo SK, Lee SK, Yeon YJ, Oh HJ, Kim SW, et al. The molecular basis of phenylketonuria in Korean. J Hum Genet; 2004. 49: 617-21.
20. 18. Kasnauskiene J, Giannattasio S, Lattanzio P, Cimbalistiene L, Kucinskas V. The molecular basis of phenylketonuria in Lithuania. Hum Mutant; 2003. 21:398-402.
21. 19. Guzzetta V, Bonapace G, Dianzani I, Parenti G, Lecora M, Giannattasio S, et al. phenylketonuria in Italy: Distinct distribution pattern of three mutations of the phenylalanine hydroxylase gene. J Inherit Metab Dis; 1997. 20:619-24.
22. 20. Rivera I, Leandro P, Lichter-Konecki U, Tavares de Almeida I, Lechner MC. Population genetics of hyperphenylalaninemia resulting from phenylalanine hydroxylase deficiency in Portugal. J Med Genet; 1998. 35:301-4.
23. 21. Dahri S, Desviat LR, Perez B, Leal F, Ugarte M, Chabraoui L. Mutation analysis of phenylketonuria patients from Morocco: High prevalence of mutation G352fsdelG and detection of a novel mutation p.K85X. Clin Biochem; 2010. 43:76-81.
24. 22. Effat L, Kuzmin A, Kasem N, Meguid NA, Kotb S, Eisensmith RC, et al. Haplotypes and mutations of the PAH locus in Egyption families with PKU. Eur J Hum Genet; 1999. 7:259-62.
25. 23. Acosta A, Silva W Jr, Carvallo T, Gomes M, Zago M. Mutations of the phenylalanine hydroxylase (PAH) gene in Brazilian patients with phenylketonuria. Hum Mutant; 2001. 17:122-30.
26. 24. Desviat LR, Perez B, Gutierrez E, Sanchez A, Barrios B, Ugarte M. Molecular basis of phenylketonuria in Cuba. Hum Mutat; 2001. 18(3): 252-252.
27. 25. Song F, Qu YJ, Zhang T, Jin YW, Wang H, Zheng XY. Phenylketonuria mutations in northern China. Mol Genet Metab; 2005. 86: 107-118.
28. 26. Hamzehloei T, Hosseini SA, Vakili R, Mojarad M. Mutation spectrum of the PAH gene in the PKU patients from Khorasan Razavi province of Iran. Gene; 2012. 506(1): 230-232.
29. 27. Alibakhshi R, Moradi K, Mohebbi Z. Mutation analysis of PAH gene in patients with PKU in western Iran and its association with polymorphisms: identification of four novel mutations. Metab Brain Dis; 2014. 29(1): 131-138.
30. 28. Razipour M, Alavinejad E, Sajedi S Z, Talebi S, Entezam M, Mohajer N, et al. Genetic study of the PAH locus in the Iranian population: familial gene mutations and minihaplotypes. Metab Brain Dis; 2017. 32(5): 1685–1691.
31. 29. Shaykholeslam Esfahani M, Vallian S. A comprehensive study of phenylalanine hydroxylase gene mutations in the Iranian phenylketonuria patients. Eur J MedGenet; https://doi.org/10.1016/ j.ejmg.2018.10.011
32. 30. Shirzad T, Saeidian A H, Bagherian H, Salehpour S, Setoodeh A, Alaei M, et al. Molecular genetics of a cohort of 635 cases of phenylketonuria in a consanguineous population. J Inherit Metab Dis; 2018 – Springer, https://doi.org/10.1007/s10545-018-0228-6.
33. 31. Bonyadi M, Omrani O, Moghanjoghi SM, Shiva S. Mutations of the phenylalanine hydroxylase gene in Iranian Azeri Turkish patients with phenylketonuria. Genet Test Mol Bioma; 2010. 14(2): 233-235.
34. 32. Vallian S, Barahimi E, Moeini H. Phenylketonuria in Iranian population: a study in institutions for mentally retarded in Isfahan. Mutat Res/Fund Mol Mech Mut; 2003. 526(1): 45-52.
35. 33. Effat LK, Essawi ML, Abd El Hamid MS, Hawari N, Gad YZ. Screening for six Mediterranean mutations in 90 Egyptian patients with phenylketonuria. Bratisl Lek Listy; 2008. 109(1):17-9.

Add your comments about this article : Your username or Email:

Send email to the article author

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

© 2024 CC BY-NC 4.0 | Razi Journal of Medical Sciences

Designed & Developed by : Yektaweb