Identification of a common 6-pyruvoyl-tetrahydropterin synthase mutation at codon 87 in Chinese phenylketonuria caused by tetrahydrobiopterin synthesis deficiency
Identification of a common 6-pyruvoyl-tetrahydropterin synthase mutation at codon 87 in Chinese phenylketonuria caused by tetrahydrobiopterin synthesis deficiency
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DOI：
10.1007/s004390050213
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发表时间：
1996-09-01
期刊：
影响因子：
5.3
通讯作者：
Hsiao, KJ
中科院分区：
文献类型：
--
作者：
Liu, TT;Hsiao, KJ
6-乙酰基-四氢蝶呤合酶（PTPS）活性的缺乏是四氢生物蝶呤（BH 4）缺乏型苯丙酮尿症的主要原因。PTPS cDNA的两个单碱基改变，核苷酸259处的C到T转变和核苷酸155处的新的A到G转变（根据cDNA序列），通过逆转录-聚合酶链反应（RT-PCR），在两个中国人PTPS缺陷同胞中鉴定出了两个PTPS基因的同源性;核苷酸259处的C-到-T转换导致密码子87处的氨基酸从脯氨酸变为丝氨酸（Pro 87 Ser），并且在核苷酸155处的A至G转变导致PTPS的密码子52处的氨基酸从天冬酰胺变为丝氨酸（Asn 52 Ser）。通过PCR扩增PTPS cDNA产物的BbvI酶切片段分析，发现C259 T错义突变占所研究的26个中国人PTPS突变等位基因的42%（11/26）。然而，在筛选的100个正常等位基因中没有发现有这种变化。提示C259 T转换可能是中国人PTPS缺陷型患者中常见的突变。
Deficiency in 6-pyruvoyl-tetrahydropterin synthase (PTPS) activity is the major cause of tetrahydrobiopterin (BH4)-deficient phenylketonuria. Two single base alterations of PTPS cDNA, a C-to-T transition at nucleotide 259 and a novel A-to-G transition at nucleotide 155 (according to cDNA sequence), were identified in two Chinese PTPS-deficient siblings by the reverse transcription-polymerase chain reaction (RT-PCR); The C-to-T transition at nucleotide 259 results in an amino acid change from proline to serine at codon 87 (Pro87Ser), and the A-to-G transition at nucleotide 155 causes an amino acid change from asparagine to serine at codon 52 (Asn52Ser) of PTPS. The C259T missense mutation can be identified by analysis of the BbvI restriction fragments of the PCR-amplified PTPS cDNA product, and was found to account for 42% (11/26) of 26 Chinese PTPS mutant alleles studied. However, none of 100 normal alleles screened were found to have this change. This result indicates that the C259T transition may be a common mutation in Chinese PTPS-deficient patients.