Yamada Yasukazu
Department of Genetics, Institute for Developmental Research, Aichi Human Service Center.
Nihon Rinsho. 2008 Apr;66(4):687-93.
Inherited mutations of a purine salvage enzyme, hypoxanthine guanine phosphoribosyltransferase (HPRT, EC 2.4.2.8; MIM308000), give rise to Lesch-Nyhan syndrome (MIM300322) or HPRT-related gout called as Kelley-Seegmiller syndrome (MIM300323). In contrast with the most severe phenotype of classical Lesch-Nyhan disease (LND), the least severe phenotype is characterized by hyperuricemia without any neurological or behavioral abnormality, and designated HPRT-related hyperuricemia (HRH). In between these two extremes are phenotypes involving hyperuricemia and varying degrees of neurobehavioral abnormality but without self-injury, designated HPRT-related neurological dysfunction (HRND). Marked genetic heterogeneity of HPRT deficiency is well known. More than 300 different mutations in the HPRT gene (HPRT1 which located in Xq26.1), deletion, insertions, duplications, abnormal splicing and point mutations at different sites of the coding region from exons 1 to 9, have been identified.
嘌呤补救酶次黄嘌呤鸟嘌呤磷酸核糖转移酶(HPRT,EC 2.4.2.8;MIM308000)的遗传性突变会引发莱施-奈恩综合征(MIM300322)或被称为凯利-西格米勒综合征(MIM300323)的HPRT相关性痛风。与经典莱施-奈恩病(LND)最严重的表型不同,最轻微的表型特征为高尿酸血症且无任何神经或行为异常,被称为HPRT相关性高尿酸血症(HRH)。介于这两种极端情况之间的是涉及高尿酸血症和不同程度神经行为异常但无自残行为的表型,被称为HPRT相关性神经功能障碍(HRND)。HPRT缺乏症存在显著的遗传异质性,这是众所周知的。已在HPRT基因(位于Xq26.1的HPRT1)中鉴定出300多种不同的突变,包括从外显子1到9的编码区不同位点的缺失、插入、重复、异常剪接和点突变。