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Mutation analysis of the phenylalanine hydroxylase gene in Azerbaijani population, a report from West Azerbaijan province of Iran.

Bagheri M, Rad IA, Jazani NH, Zarrin R, Ghazavi A - Iran J Basic Med Sci (2015)

Bottom Line: The mutations of R243Q, 364delG, L333F, 261X, I65T, and R408W were not detected in our samples.It can be concluded that the IVS10-11 mutation has the highest frequency in the tested population.To our knowledge, this report is the first in its own kind and provides better understanding of the genetic heterogeneity, the origin and distributions of PAH mutations in West Azerbaijan province of Iran.

View Article: PubMed Central - PubMed

Affiliation: Food and Beverages Safety Research Center, Urmia University of Medical Sciences, Urmia, Iran ; Genetics Department, Urmia University of Medical Sciences, Urmia, Iran ; Cellular and Molecular Research Center, Urmia University of Medical Sciences, Urmia, Iran.

ABSTRACT

Objectives: Phenylketonuria (PKU) is a genetic inborn error of phenylalanine (Phe) metabolism resulting from insufficiency in the hepatic enzyme, phenylalanine hydroxylase (PAH), which leads to elevated levels of Phe in the blood. The present study was carried out for mutation analysis of the PAH gene in West Azerbaijan province of Iran.

Materials and methods: A total of 218 alleles from 40 PKU families were studied using restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) method.

Results: The frequencies of IVS10-11, S67P, R261Q, R252W, IVS11nt-1 g>c, R408Q, and Q232Q mutations were 28(35), 17(21.25), 15(18.75), 3(3.75), 3(3.75), 2(2.5), and 1(1.25), in cases group, and 51(23.4), 31(14.2), 27(12.4), 6(2.75), 6(2.75), 4(1.83), and 2(0.92) in total group, respectively. The mutations of R243Q, 364delG, L333F, 261X, I65T, and R408W were not detected in our samples.

Conclusion: It can be concluded that the IVS10-11 mutation has the highest frequency in the tested population. To our knowledge, this report is the first in its own kind and provides better understanding of the genetic heterogeneity, the origin and distributions of PAH mutations in West Azerbaijan province of Iran.

No MeSH data available.


Related in: MedlinePlus

Detection of S67P mutation in 11 samples. PCR products (463 bp) were digested with XbaI. The presence of S67P mutation removes restriction site for XbaI enzymeIndividuals homozygous for S67P mutation show a single un-cut band of 463 bp. Individuals heterozygous for S67P mutation show three bands of 463, 348 and 115 bpLane M: 50 bp marker (Fermentas). Lanes 1,2,4,5,10: Heterozygous for S67P mutation. Lanes 3,6,7,8: Normal sequence
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Figure 5: Detection of S67P mutation in 11 samples. PCR products (463 bp) were digested with XbaI. The presence of S67P mutation removes restriction site for XbaI enzymeIndividuals homozygous for S67P mutation show a single un-cut band of 463 bp. Individuals heterozygous for S67P mutation show three bands of 463, 348 and 115 bpLane M: 50 bp marker (Fermentas). Lanes 1,2,4,5,10: Heterozygous for S67P mutation. Lanes 3,6,7,8: Normal sequence

Mentions: Totally, 218 chromosomes from 40 PKU families were studied. Results of the present investigation are summarized in Tables 2 and 3. The rate of consanguineous marriages was 47.5% (19/40) among all studied families. The frequencies of IVS10-11, S67P, R261Q, R252W, IVS11nt-1 g>c, R408Q, and Q232Q mutations were 28(35), 17(21.25), 15(18.75), 3(3.75), 3(3.75), 2(2.5), and 1(1.25), in case group and 51(23.4), 31(14.2), 27(12.4), 6(2.75), 6(2.75), 4(1.83), and 2(0.92) in total group, respectively. Observed mutations in the patients were inherited from their parents. The mutations of R243Q, 364delG, L333F, 261X, I65T, and R408W were not found in this study. Of the alleles studied, the most frequent mutation was IVS10nt546 (35%). Seven mutations represent approximately 86.25% and 83% of PKU chromosomes analyzed in cases and total groups, respectively. Our analysis showed that 37.5% (15/40) and 62.5% (25/40) of the cases have homozygote and compound heterozygote genotypes regarding the studied mutations (Table 3). The most common mutations of IVS10-11, S67P, and R261Q can be as a result of the high rate of consanguineous marriages. The frequencies of missense, splice, and silent mutations were 37 (46.25), 31 (38.75), and 1 (1.25), in cases and 68 (31.18), 57 (26.15), and 2 (0.92) in total groups, respectively. Deletion and nonsense mutations were not identified in this investigation. Figures 1 to 4 show PKU mutation analysis in this local population.


Mutation analysis of the phenylalanine hydroxylase gene in Azerbaijani population, a report from West Azerbaijan province of Iran.

Bagheri M, Rad IA, Jazani NH, Zarrin R, Ghazavi A - Iran J Basic Med Sci (2015)

Detection of S67P mutation in 11 samples. PCR products (463 bp) were digested with XbaI. The presence of S67P mutation removes restriction site for XbaI enzymeIndividuals homozygous for S67P mutation show a single un-cut band of 463 bp. Individuals heterozygous for S67P mutation show three bands of 463, 348 and 115 bpLane M: 50 bp marker (Fermentas). Lanes 1,2,4,5,10: Heterozygous for S67P mutation. Lanes 3,6,7,8: Normal sequence
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4556756&req=5

Figure 5: Detection of S67P mutation in 11 samples. PCR products (463 bp) were digested with XbaI. The presence of S67P mutation removes restriction site for XbaI enzymeIndividuals homozygous for S67P mutation show a single un-cut band of 463 bp. Individuals heterozygous for S67P mutation show three bands of 463, 348 and 115 bpLane M: 50 bp marker (Fermentas). Lanes 1,2,4,5,10: Heterozygous for S67P mutation. Lanes 3,6,7,8: Normal sequence
Mentions: Totally, 218 chromosomes from 40 PKU families were studied. Results of the present investigation are summarized in Tables 2 and 3. The rate of consanguineous marriages was 47.5% (19/40) among all studied families. The frequencies of IVS10-11, S67P, R261Q, R252W, IVS11nt-1 g>c, R408Q, and Q232Q mutations were 28(35), 17(21.25), 15(18.75), 3(3.75), 3(3.75), 2(2.5), and 1(1.25), in case group and 51(23.4), 31(14.2), 27(12.4), 6(2.75), 6(2.75), 4(1.83), and 2(0.92) in total group, respectively. Observed mutations in the patients were inherited from their parents. The mutations of R243Q, 364delG, L333F, 261X, I65T, and R408W were not found in this study. Of the alleles studied, the most frequent mutation was IVS10nt546 (35%). Seven mutations represent approximately 86.25% and 83% of PKU chromosomes analyzed in cases and total groups, respectively. Our analysis showed that 37.5% (15/40) and 62.5% (25/40) of the cases have homozygote and compound heterozygote genotypes regarding the studied mutations (Table 3). The most common mutations of IVS10-11, S67P, and R261Q can be as a result of the high rate of consanguineous marriages. The frequencies of missense, splice, and silent mutations were 37 (46.25), 31 (38.75), and 1 (1.25), in cases and 68 (31.18), 57 (26.15), and 2 (0.92) in total groups, respectively. Deletion and nonsense mutations were not identified in this investigation. Figures 1 to 4 show PKU mutation analysis in this local population.

Bottom Line: The mutations of R243Q, 364delG, L333F, 261X, I65T, and R408W were not detected in our samples.It can be concluded that the IVS10-11 mutation has the highest frequency in the tested population.To our knowledge, this report is the first in its own kind and provides better understanding of the genetic heterogeneity, the origin and distributions of PAH mutations in West Azerbaijan province of Iran.

View Article: PubMed Central - PubMed

Affiliation: Food and Beverages Safety Research Center, Urmia University of Medical Sciences, Urmia, Iran ; Genetics Department, Urmia University of Medical Sciences, Urmia, Iran ; Cellular and Molecular Research Center, Urmia University of Medical Sciences, Urmia, Iran.

ABSTRACT

Objectives: Phenylketonuria (PKU) is a genetic inborn error of phenylalanine (Phe) metabolism resulting from insufficiency in the hepatic enzyme, phenylalanine hydroxylase (PAH), which leads to elevated levels of Phe in the blood. The present study was carried out for mutation analysis of the PAH gene in West Azerbaijan province of Iran.

Materials and methods: A total of 218 alleles from 40 PKU families were studied using restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) method.

Results: The frequencies of IVS10-11, S67P, R261Q, R252W, IVS11nt-1 g>c, R408Q, and Q232Q mutations were 28(35), 17(21.25), 15(18.75), 3(3.75), 3(3.75), 2(2.5), and 1(1.25), in cases group, and 51(23.4), 31(14.2), 27(12.4), 6(2.75), 6(2.75), 4(1.83), and 2(0.92) in total group, respectively. The mutations of R243Q, 364delG, L333F, 261X, I65T, and R408W were not detected in our samples.

Conclusion: It can be concluded that the IVS10-11 mutation has the highest frequency in the tested population. To our knowledge, this report is the first in its own kind and provides better understanding of the genetic heterogeneity, the origin and distributions of PAH mutations in West Azerbaijan province of Iran.

No MeSH data available.


Related in: MedlinePlus