Characterization of mutations in phenotypic variants of hypoxanthine phosphoribosyltransferase deficiency.
Characterization of mutations in phenotypic variants of hypoxanthine phosphoribosyltransferase deficiency.
复制标题
次黄嘌呤磷酸核糖转移酶缺陷表型变异突变的表征。
DOI：
10.1093/hmg/1.6.427
复制
发表时间：
1992
影响因子：
3.5
通讯作者：
Nyhan,WL
中科院分区：
文献类型：
--
作者：
Sege-Peterson,K;Chambers,J;Page,T;Jones,OW;Nyhan,WL
莱-尼二氏病是由于几乎完全缺乏次黄嘌呤-鸟嘌呤磷酸核糖转移酶（HPRT）引起的。部分HPRT缺陷，与不太严重的表型，也已确定。我们的特点是突变发生在HPRT cDNA分离的HPRT缺乏症患者，重点是检查更不寻常的部分变异的HPRT缺乏症。通过PCR扩增HPRT cDNA，克隆并通过自动DNA序列分析进行分析。研究了22名HPRT缺乏症的无关个体，包括8名经典的Lesch-Nyhan患者和14名代表部分HPRT缺乏症的不同人群的患者。我们发现了一种多样的突变模式，点突变占大多数异常HPRT基因。无义突变和外显子缺失仅见于经典型Lesch-Nyhan患者的HPRT cDNA。与部分HPRT缺陷相关的突变通常位于分子的氨基末端部分。在HPRT蛋白中Arg-51的位置处鉴定出CpG突变热点。两个高尿酸血症患者表现出不寻常的剪接位点突变：在一个，这导致创建一个额外的外显子在HPRT基因和外显子6的另一部分是在一个亚群的成绩单中失踪，产生显性，负突变的效果。
The Lesch—Nyhan disease is caused by an almost complete lack of the enzyme hypoxanthine-guanine phosphoribosyl-transferase (HPRT). Partial HPRT-deficiency, associated with less severe phenotype, has also been identified. We have characterized mutations occurring in HPRT cDNA isolated from patients with HPRT-deficiency with an emphasis on examining the more unusual partial variants of HPRT-deficiency. HPRT cDNA was amplified by PCR, cloned and analyzed by automated DNA sequence analysis. Twenty-two, unrelated individuals with HPRT deficiency were studied including eight classic Lesch—Nyhan patients and fourteen patients representing the different groups of partial HPRT deficiency. We found a diverse pattern of mutations with point mutations accounting for the majority of abnormal HPRT genes. Nonsense mutations and exon deletions were only found in HPRT cDNA isolated from classic Lesch—Nyhan patients. Mutations associated with partial HPRT-deficiency were frequently located in the amino terminal part of the molecule. A CpG mutational hot spot was identified at the position for Arg-51 in the HPRT protein. Two hyperuricemic patients exhibited unusual splice site mutations: in one this led to the creation of an additional exon in the HPRT gene and in the other part of exon 6 was missing in a subpopulation of the transcripts, producing the effect of a dominant, negative mutation.