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A novel large deletion (exons 12, 13) and a missense mutation (p.G46R) in the PAH in a Japanese patient with phenylketonuria
Yoshihiro Maruo, Masafumi Suzaki, Katsuyuki Matsui, Yu Mimura, Asami Mori, Haruo Shintaku, Yoshihiro Takeuchi
Shiga, Japan
Author Affiliations: Department of Pediatrics (Maruo Y, Matsui K, Mimura Y, Mori A, Takeuchi Y) and Central Research Laboratory (Suzaki M), Shiga University of Medical Science, Tsukinowa, Seta, Otsu, Shiga 520-2192, Japan; Department of Pediatrics, Osaka City University Graduate School of Medicine, Osaka, Japan (Shintaku H)
Corresponding Author: Yoshihiro Maruo, MD, PhD, Department of Pediatrics, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, Shiga 520-2192, Japan (Tel: +81-77-548-2228; Fax: +81-77-548-2230; Email: maruo@belle.shiga-med.ac.jp)
doi: 10.1007/s12519-015-0020-8
Background: Phenylketonuria (PKU) is caused by a defect in phenylalanine hydroxylase (PAH). More than 500 mutations have been reported for the gene encoding PAH. However, approximately 1%¨C5% of these include large deletions and large duplications that cannot be detected by conventional methods.
Methods: In this report we tried to fully characterize a PAH-deficient patient. The patient was a 2-year-old Japanese boy who was diagnosed with classical PKU at the time of neonatal screening, which was confirmed by the tetrahydrobiopterin-loading test. PCR-related direct sequencing and multiplex ligation-dependent probe amplification (MLPA) were used to analyze of the PAH of the patient.
Results: Using PCR-related direct sequencing method, we could detect only a heterozygous novel missense mutation: p.136G>C (p.G46R). A second mutation was detected by MLPA. The patient was heterozygous for a novel large deletion of exons 12 and 13: c.1200-?_1359+?del (EX12_13del). For genetic counseling, an accurate genetic diagnosis is often necessary.
Conclusions: Through a combination of MLPA and conventional methods, the success rate of PAH mutation identification can be close to 100%.
World J Pediatr 2015;11(2):181-184
Key words: large deletion;
multiplex ligation-dependent probe
amplification;
phenylalanine hydroxylase;
phenylketonuria
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