Abstract
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%–5% 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%.
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Maruo, Y., Suzaki, M., Matsui, K. et al. A novel large deletion (exons 12, 13) and a missense mutation (p.G46R) in the PAH in a Japanese patient with phenylketonuria. World J Pediatr 11, 181–184 (2015). https://doi.org/10.1007/s12519-015-0020-8
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DOI: https://doi.org/10.1007/s12519-015-0020-8