Molecular analysis of two enzyme genes, HPRT1 and PRPS1, causing X-Hnked inborn errors of purine metabolism.
Molecular analysis of two enzyme genes, HPRT1 and PRPS1, causing X-Hnked inborn errors of purine metabolism.
复制标题
对导致嘌呤代谢 X-Hnked 先天性错误的两种酶基因 HPRT1 和 PRPS1 进行分子分析。
DOI：
10.1080/15257771003738691
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Wakamatsu N
中科院分区：
文献类型：
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作者：
Yamada Y;Yamada K;Nomura N;Yamano A;Kimura R;Tomida S;Naiki M;Wakamatsu N
次黄嘌呤鸟嘌呤磷酸核糖转移酶（HPRT）的遗传突变引起Lesch-Nyhan综合征或HPRT相关痛风。另一方面，PRPS 1突变导致PRPP合成酶超活性与高尿酸血症和痛风，有时包括神经发育异常。在我们上次报告后，我们已经确定了两个Lesch-Nyhan家族的两个突变。其中1例在HPRT 1基因外显子2上发现了一个新的单核苷酸替换（130 G>T），导致错义突变D44 Y。RT-PCR扩增结果显示，除了正常大小的cDNA片段外，还有少量较短的片段跳过外显子2和3。另一个错义突变F74 L（222 C> A）在日本患者中检测到，但以前在欧洲家族中也有报道。在4例伴有轻度神经系统异常的高尿酸血症患者中，未发现HPRT 1中导致部分HPRT缺陷的突变。在这4例患者中，我们也进行了PRPS 1的分子分析，但没有发现PRPP合成酶的突变。
Inherited mutation of hypoxanthine guanine phosphoribosyltransferase (HPRT) gives rise to Lesch-Nyhan syndrome or HPRT-related gout. On the other hand, PRPS1 mutations cause PRPP synthetase superactivity associated with hyperuricemia and gout, sometimes including neurodevelopmental abnormalities. We have identified two mutations in two Lesch-Nyhan families after our last report. One of them, a new single nucleotide substitution (130G>T) resulting in a missense mutation D44Y was detected in exon 2 of HPRT1. RT-PCR amplification showed not only a cDNA fragment with normal size, but also a small amount of shorter fragment skipping exons 2 and 3. The other missense mutation F74L (222C > A) was detected in a Japanese patient but has been reported previously in European families. In four hyperuricemic patients with mild neurological abnormality, no mutations responsible for partial HPRT deficiency were identified in HPRT1. In these four patients, we also performed molecular analysis of PRPS1, but no mutations in PRPP synthetase were found.