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First Case Report of EX3del4765 Mutation in PAH Gene in Asian Population.

Soltani Z, Karami F, Yassaee V, Hashemi Gorji F, Talebzadeh M, Miryounesi M - Iran Red Crescent Med J (2016)

Bottom Line: Most of the PAH mutations are missense mutations (67%), which are followed by small or large deletions (13%).This is the first case report of EX3del4765 in Asian patients with PKU.This finding may help improve early detection, differential diagnosis, genetic counseling, and even treatment of patients with PKU.

View Article: PubMed Central - PubMed

Affiliation: Genomic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.

ABSTRACT

Introduction: Phenylketonuria (PKU) is an autosomal recessive inborn error of phenylalanine metabolism, which is caused by mutation in phenylalanine hydroxylase (PAH) gene. Most of the PAH mutations are missense mutations (67%), which are followed by small or large deletions (13%).

Case presentation: We reported a patient with classic PKU and his parents harboring a large deletion in exon 3 (EX3del4765) of PAH gene. This is the first case report of EX3del4765 in Asian patients with PKU.

Conclusions: This finding may help improve early detection, differential diagnosis, genetic counseling, and even treatment of patients with PKU.

No MeSH data available.


Related in: MedlinePlus

A, gel electrophoresis of PCR products of exon 2 and 3; 1, absence of exon 3 in patient, 2 and 3, presence of exon 3 in the father and mother. B, gel electrophoresis of PCR products using primers for introns 2 and 3; 1, 1120 base pair band due to deletion in patient; 2, absence of the band in normal control; 3 and 4, presence of the band in heterozygous father and mother.
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fig24908: A, gel electrophoresis of PCR products of exon 2 and 3; 1, absence of exon 3 in patient, 2 and 3, presence of exon 3 in the father and mother. B, gel electrophoresis of PCR products using primers for introns 2 and 3; 1, 1120 base pair band due to deletion in patient; 2, absence of the band in normal control; 3 and 4, presence of the band in heterozygous father and mother.

Mentions: Molecular genetic analysis was performed to confirm PKU diagnosis in the child. After obtaining approval from the Medical Ethics Committee of Shahid Beheshti University of Medical Sciences, and informed consent from patient family, peripheral blood samples from the patient and his parents were collected. Genomic DNA was extracted by salting out method. Extracted genomic DNA was amplified by polymerase chain reaction (PCR) technique by ABI GeneAmp 9700 device, using PAH gene primers amplifying exons 1 - 13 and exon-intron boundaries. Then, PCR products were sequenced using the ABI Prism 3130 Genetic Analyzer (Applied Biosystems, Foster City, CA, USA) (Primer sequences and PCR programs are available upon request). During PCR of PAH exons in the patient, exon 3 was not amplified. Further analysis was conducted by designing two primers within the flanking introns of exon 3 (introns 2 and 3). In normal individuals, the segment size between two primers is 5885 bps (which does not amplify in regular PCR). In our patient, a 1120 bps segment was amplified (Figure 2) that demonstrated a large deletion of 4765 bps (g.21560-26324del4765) containing exon 3, and results were confirmed by Sanger sequencing (Figure 3) too. As a result, heterozygous status of parents for the same deletion was revealed by genotyping analysis.


First Case Report of EX3del4765 Mutation in PAH Gene in Asian Population.

Soltani Z, Karami F, Yassaee V, Hashemi Gorji F, Talebzadeh M, Miryounesi M - Iran Red Crescent Med J (2016)

A, gel electrophoresis of PCR products of exon 2 and 3; 1, absence of exon 3 in patient, 2 and 3, presence of exon 3 in the father and mother. B, gel electrophoresis of PCR products using primers for introns 2 and 3; 1, 1120 base pair band due to deletion in patient; 2, absence of the band in normal control; 3 and 4, presence of the band in heterozygous father and mother.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4862320&req=5

fig24908: A, gel electrophoresis of PCR products of exon 2 and 3; 1, absence of exon 3 in patient, 2 and 3, presence of exon 3 in the father and mother. B, gel electrophoresis of PCR products using primers for introns 2 and 3; 1, 1120 base pair band due to deletion in patient; 2, absence of the band in normal control; 3 and 4, presence of the band in heterozygous father and mother.
Mentions: Molecular genetic analysis was performed to confirm PKU diagnosis in the child. After obtaining approval from the Medical Ethics Committee of Shahid Beheshti University of Medical Sciences, and informed consent from patient family, peripheral blood samples from the patient and his parents were collected. Genomic DNA was extracted by salting out method. Extracted genomic DNA was amplified by polymerase chain reaction (PCR) technique by ABI GeneAmp 9700 device, using PAH gene primers amplifying exons 1 - 13 and exon-intron boundaries. Then, PCR products were sequenced using the ABI Prism 3130 Genetic Analyzer (Applied Biosystems, Foster City, CA, USA) (Primer sequences and PCR programs are available upon request). During PCR of PAH exons in the patient, exon 3 was not amplified. Further analysis was conducted by designing two primers within the flanking introns of exon 3 (introns 2 and 3). In normal individuals, the segment size between two primers is 5885 bps (which does not amplify in regular PCR). In our patient, a 1120 bps segment was amplified (Figure 2) that demonstrated a large deletion of 4765 bps (g.21560-26324del4765) containing exon 3, and results were confirmed by Sanger sequencing (Figure 3) too. As a result, heterozygous status of parents for the same deletion was revealed by genotyping analysis.

Bottom Line: Most of the PAH mutations are missense mutations (67%), which are followed by small or large deletions (13%).This is the first case report of EX3del4765 in Asian patients with PKU.This finding may help improve early detection, differential diagnosis, genetic counseling, and even treatment of patients with PKU.

View Article: PubMed Central - PubMed

Affiliation: Genomic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.

ABSTRACT

Introduction: Phenylketonuria (PKU) is an autosomal recessive inborn error of phenylalanine metabolism, which is caused by mutation in phenylalanine hydroxylase (PAH) gene. Most of the PAH mutations are missense mutations (67%), which are followed by small or large deletions (13%).

Case presentation: We reported a patient with classic PKU and his parents harboring a large deletion in exon 3 (EX3del4765) of PAH gene. This is the first case report of EX3del4765 in Asian patients with PKU.

Conclusions: This finding may help improve early detection, differential diagnosis, genetic counseling, and even treatment of patients with PKU.

No MeSH data available.


Related in: MedlinePlus