A novel large deletion (exons 12, 13) and a missense mutation (p.G46R) in the PAH in a Japanese patient with phenylketonuria.
A novel large deletion (exons 12, 13) and a missense mutation (p.G46R) in the PAH in a Japanese patient with phenylketonuria.
复制标题
日本苯丙酮尿症患者 PAH 中出现新的大缺失（外显子 12、13）和错义突变（p.G46R）。
DOI：
10.1007/s12519-015-0020-8
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Takeuchi Y.
中科院分区：
文献类型：
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作者：
Maruo Y;Suzaki M;Matsui K;Mimura Y;Mori A;Shintaku H;Takeuchi Y.
苯丙酮尿症（PKU）是由苯丙氨酸羟化酶（PAH）缺陷引起的。据报道，编码PAH的基因有500多个突变。然而，其中约1%-5%包括大的缺失和大的重复，不能通过常规methods.MethodsIn这份报告中，我们试图充分表征PAH缺陷的患者。该患者是一名2岁的日本男孩，在新生儿筛查时被诊断为经典PKU，并通过四氢生物蝶呤负荷试验证实。结果PCR相关直接测序法仅检测到一个新的错义突变：p.136G>C（p.G46R）。MLPA检测到第二个突变。该患者为外显子12和13新型大缺失杂合子：c.1200-？_ 1359+？del（EX12_13del）。结论通过MLPA与常规方法相结合，PAH基因突变鉴定的成功率接近100%。
BackgroundPhenylketonuria (PKU) is caused by a defect in phenylalanine hydroxylase (PAH). More than 500 mutations have been reported for the gene encodingPAH. However, approximately 1%–5% of these include large deletions and large duplications that cannot be detected by conventional methods.MethodsIn this report we tried to fully characterize aPAH-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 thePAHof the patient.ResultsUsing 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.ConclusionsThrough a combination of MLPA and conventional methods, the success rate ofPAHmutation identification can be close to 100%.