G6PD缺陷症的分子基础

Ｇ６ＰＤ基因的克隆和有关其结构方面的最新研究进展已使用阐明此酶缺陷及多态性的分子基础成为可能。     

人类G6PD及其缺陷研究进展

Ｇ６ＰＤ是磷酸戊糖旁路代谢的限速酶，了是重要的看家酶。Ｇ６ＰＤ缺陷症是人类最常见的遗传性疾病。本仅就Ｇ６ＰＤ的基因结构、蛋白表达、突变型研究及与疾病的关系进行了综述。     

人类G6PD缺乏症的分子生物学研究进展

人类Ｇ_６ＰＤ缺乏症的分子生物学研究进展杨明综述杜传书审校葡萄糖－６－磷酸脱氢酶（Ｇ６ＰＤ）缺乏症是一类累及约２亿人的Ｘ连锁不完全显性遗传病［１，２］，在临床上表现为新生儿黄疸、慢性非球形细胞性溶血性贫血（ＣＮＳＨＡ）、蚕豆病和药物诱导性溶血。目前已?..     

地中海贫血伴G6PD缺陷临床研究报告

地中海贫血（地贫）与红细胞葡萄糖6磷酸脱氢酶（G6PD）缺陷，在我国华南地区尤为广东较为多见。现将11例地中海贫血其中α—地贫4例，β—地贫7例合并G6PD缺陷分析如下。     

1600例早孕夫妇红细胞G6PD检测分析

本文采用Ｇ６ＰＤ荧光斑点试验作定性初筛，Ｇ６ＰＤ／６ＰＧＤ比值法作定量确诊。从１９９６ 年９ 月至１９９８ 年６ 月对珠海地区１６００ 例早孕夫妇进行了红细胞Ｇ６ＰＤ检测。查出不同程度缺乏者７６ 人，检出率为４－７５ ％ 。其中夫妇双方均缺乏者１２ 对，占３１－５８％ ，而且珠海籍的人群发生率最高（８－０９％ ），其它广东籍人群次之（７－７６％ ），非广东籍人群最低（２－１８％ ）。结果表明在该市婚前体格和早孕建卡期开展Ｇ６ＰＤ缺乏症的筛查工作是非常重要的。同时加强孕期保健宣教和指导，提高携带者的防患意识，避免受到氧化性物质的损害，对优生优育同样具有重要意义。     

云南省两种G6PD基因突变的检测

红细胞葡萄糖 - 6 -磷酸脱氢酶 (glucose- 6 - phosphatedehydrogenase,G6 PD) ,是磷酸戊糖旁路中产生还原型辅酶 (reduced nicotinamide adenine dinucleotide phosphate,NADPH)的关键酶。G6 PD的缺陷可导致蚕豆病、药物性溶血、新生儿高胆红素血症乃至核黄疸、感染性溶血及非球形细胞溶血性贫血等 ,G6 PD缺乏症是一种常见的人类遗传性酶缺陷疾病。G6 PD基因突变是导致 G6 PD缺乏症的主要分子基础 ,目前已发现 DNA突变类型 78种 ,其中在中国人中发现了 13种[1 ] 。云南是 G6 PD缺乏症高发区 ,部分少数民族地区该病发生率达16 .…     

G6PD缺乏会增加乙型肝炎病毒感染吗？

本文对珠海地区Ｇ６ＰＤ缺乏症进行了调查，其发生率为２．９２％，基因频率为０．０１９６。并发现Ｇ６ＰＤ缺乏患者乙型肝炎病毒感染的机会比正常人高２倍，提示此病能增加某些疾病的易感性。     

G6PD试纸法与G6PD/6PGD 比值法的对照研究

目的 通过G6PD试纸法与G6PD／6PGD比值法的对比，探讨应用G6PD试纸法的可行性。方法 同时用G6PD试纸法与G6PD／6PGD比值法对115名广东籍儿童进行G6PD缺乏定性检查，观察两种方法的优缺点。结果 本组病例G6PD缺乏症患者的检出率，两种方法的符合率100％，而杂合子的诊断G6PD试纸法可提供，G6PD／6PGD比值法未能提供。结论 G6PD试纸法使用方便简单，快速，且可以检出杂合子，尤其适合普查及不易抽静脉血的新生儿，婴幼儿及危重病人。     

1478例育龄男女G6PD缺乏的筛查研究

红细胞葡萄糖６－磷酸脱氢酶（Ｇ６ＰＤ）缺乏症是我国华南地区最常见的遗传性溶血性疾病，临床上可按酶的缺乏程度将此病分为二类：一类平时无溶血症状，但在某些诱因作用下发生溶血性反应；另一类在无诱因情况下出现慢性溶血，我国大多数病例属第一种。广东省发病率仅次...     

云南两边境州6民族0～6岁儿童G6PD缺乏症的流行病学调查研究

目的了解德宏州、西双版纳州的6种少数民族G6PD缺乏症的现况,为其防治提供科学依据。方法西双版纳州采用G6PD荧光斑点试验,德宏州采用改良G6PD/6PGD定量比值法。统计学处理：采用SPSS13/PEMS3.软件,计数资料用χ2检验,并进行多因素Logistic分析。结果 1.不同年龄G6PD缺乏率各年龄组无明显差异;2.不同性别G6PD缺乏有明显差异,男童6.3%,女童1.9%,男童明显高于女童;3.不同地区同一民族比较：版纳州傣族阳性率为2.5%,德宏州傣族阳性率为6.8%,德宏州明显高于版纳州;4.不同民族比较：G6PD缺乏率以德昂族居首,其后依次为：阿昌族7.1%、景颇族、汉族及其他民族5.0%,傣族4.0%、布朗族0.4%。两两比较各民族之间差异有显著意义P〈0.001;5.多因素分析：显示不同州有差异,同一州不同县市也有差异,都是危险因素。结论 1.进行人群筛检以发现携带者,从而降低G6PD的发生率;2.地区影响大于民族影响。     

Characterization of G6PD deficiency in southern Croatia: description of a new variant, G6PD Split

Glucose-6-phosphate dehydrogenase (G6PD) deficiency protects from severe forms of malaria. It is interesting therefore to analyze the molecular basis underlying G6PD deficiency in regions such as the Mediterranean basin where malaria was present for a long time in history. Here we report on the genetic characterization of G6PD deficiency among inhabitants of one Mediterranean region-the Dalmatian region of south Croatia. We analyzed 24 unrelated G6PD-deficient male subjects. Molecular testing revealed several different mutations: G6PD Cosenza 9, G6PD Mediterranean 4, G6PD Seattle 3, G6PD Union 3, and G6PD Cassano 1. Furthermore, we have identified one novel G6PD variant that we named G6PD Split. This variant is caused by a nucleotide change 1442 C-->G leading to the amino acid substitution 481 Pro-->Arg and is characterized by moderate enzyme deficiency (class III variant). This study reveals a higher prevalence (37.5%) of the Cosenza mutation in the Dalmatian region than anywhere else previously investigated and overall shows the considerable molecular heterogeneity underlining G6PD deficiency that can be observed in Mediterranean populations.     

7488例育龄人群G6PD缺乏症检查结果分析

目的了解广东地区G6PD缺乏症的发病情况.方法用G6PD/6PGD比值法.对7488例育龄人群进行了红细胞葡萄糖6-磷酸脱氢酶缺乏症临床检测.结果在7488例受检者中,共检出G6PD缺乏者488例,发生率为6.52%.结论广东是G6PD缺乏症的高发区,应在全省各地普及推广G6PD缺乏的大人群筛查,尤其是育龄人群的筛查.     

"地贫"合并G6PD缺陷症G6PD活性的实验研究

目的探讨地中海贫血(地贫)及地贫合并G6PD缺陷症的G6PD活性范围,提高女性地贫合并G6PD缺陷者的诊断率。方法用GAP-PCR法检测α-THAL基因:反向点杂交(RDB)法检测β-THAL基因及家系来验证用电泳法发现的各种地贫;用G6PD/6PGD酶直接比值法(紫外比值法)及家系来确诊G6PD缺陷症。结果重型β地贫、HBH病、轻型β、轻型α地贫的G6PD活性分别是正常人的3倍以上、2~3倍、2倍、1.5倍;地贫合并G6PD缺陷的女性杂合子62%以上G6PD活性在正常范围。结论1.地贫合并G6PD缺陷的女性杂合子,若单纯检测G6PD活性,漏诊达62%,用紫外比值法90%可以检出;2.部分地贫合并G6PD缺陷症的女性杂合子,如果G6PD/6PGD比值结果在1.01-1.06之间,做家系G6PD检测或基因检测,可避免漏诊。     

Molecular variants of G6PD deficiency among certain tribal communities of Orissa,India

This study investigated the extent of molecular heterogeneity of the G6PD enzyme among certain aboriginal (tribal) populations of Orissa, an eastern Indian state, which is hyperendemic for Plasmodium falciparum malaria. A total of 3480 males from 14 tribal communities were screened, and 223 (6.4%) individuals were found to be G6PD deficient. Molecular analysis revealed that 59.2% of deficient individuals had the G6PD Orissa mutation and 37.2% had the G6PD Mediterranean mutation. The presence of G6PD Med has not been previously reported among the tribal populations of Orissa. Interestingly, both G6PD Med and G6PD Orissa were found among communities belonging to the Mundari (Austroasiatic) linguistic group, while G6PD Med was exclusive to Dravidian and G6PD Orissa to Indo-Aryan groups. Erythrocytic G6PD enzyme activity was severely reduced in the case of G6PD Med type (0.64–1.1 IU/g Hb) as well as among the uncharacterized samples, but was moderate in G6PD Orissa type (1.2–3.1 IU/g Hb). Anaemia was moderate among the individuals with G6PD Med mutation and mild among individuals with G6PD Orissa mutations. The prevalence of G6PD deficiency as well as molecular variants of the Gd^– gene is highly heterogeneous among the tribal population of Orissa. The high endemicity of P. falciparum malaria has probably selected two different molecular variants of Gd^– at different points in time, which is discussed.     

比值法和基因检测G6PD酶活性的对比分析

目的对G6P／6PD比值法和基因两种不同的方法检测G6PD酶活性进行对比分析,评价其准确性和特异性。方法对来我院门诊就诊的G6PD缺乏儿童及新生儿疾病筛查初筛阳性召回的新生儿共91例,用G6W6PG比值法和基因进行G6PD酶活性检测,对这两种方法进行对比分析。结果91例患儿中,比值法检测,G6P／6PG小于正常值75例,正常16例。基因突变检测法,74例被检出存在基因突变,17例未检测到突变。结论两种方法无统计学差异。比值法可作为一种常规的筛查方法,经济实惠,可以推广到基层;而基因确诊费用昂贵,但作为分子水平诊断的方法,能够精确找到突变住点,更有利于指导临床用药,成为今后的发展方向。     

应用荧光斑点法和比值法检测G6PD

目的建立适合于G6PD缺乏的新生儿筛查及确诊方法。方法应用荧光斑点法(FST)对新生儿筛查滤纸干血片进行检测，对可疑阳性者召回，抽静脉血以D6PD／6PGD比值法进行确诊，同时结合新生儿父母亲的G6PD结果，根据遗传关系综合分析。结果FST筛查25000例新生儿，G6PD缺乏阳性率为4．56％，确诊检出率为4．09％。与比值法的符合率为90．4％，G6PD重度缺乏者的符合率为100％，G6PD中间缺乏者的符合率为78．5％，室间质量控制结果与反馈结果符合率为100％。结论FST汀具有高的敏感性、特异性和准确性，方法简便、快捷、费用低廉，可对滤纸干血片标本进行大规模的筛查检测，同时利用比值法进行确诊，可减少假阳性及假阴性，有利于早期诊断和防治G6PD缺乏所致的新生儿黄疸和急性溶血。     

荧光测定法定量测定滤纸片干血斑标本G6PD酶活性的可靠性分析

目的探讨荧光测定法测定滤纸片干血斑标本G6PD酶活性的可靠性。方法随机选取43例门诊孕前咨询者为检测对象,每人采集2ml静脉血抗凝保存同时制备滤纸片干血斑标本。采用G6PD/6PGD比值法测定抗凝血G6PD/6PGD比值,同时采用荧光测定法定量测定滤纸片干血斑标本G6PD酶活性,比较两种方法测定结果。结果荧光测定法检测43份滤纸片干血斑标本,检出1例缺乏（1.57 IU/gHb）;比值法检测43份抗凝血标本,检出1例缺乏（0.76）;两种方法符合率为100%。结论荧光测定法定量测定G6PD酶活性准确性高、简单、快捷、费用低廉,可对滤纸片干血斑标本进行G6PD缺乏症的大规模筛查,适于在G6PD缺乏高发区推广应用。     

东莞地区2399例育龄夫妇G6PD缺乏症的筛查结果分析

目的了解东莞地区葡萄糖-6-磷酸脱氢酶（G6PD）缺乏症的发病情况。方法用G6PD/6PGD定量比值法对2399例新婚对象进行红细胞G6PD缺乏的临床检测。结果在2399例受检者中,G6PD缺乏者99例,发生率为4.13%（99/2399）。男性51例,占男性受检人数的4.57%（51/1117）;女性48例,占女性受检人数的3.74%（48/1282）。结论东莞地区是G6PD缺乏症的高发区,应在全市各地普及推广G6PD的大人群筛查,尤其是育龄夫妇的筛查。     

Glucose‐6‐phosphate dehydrogenase (G6PD) variants in Malaysian Chinese

We screened 38 G6PD‐deficient male Chinese neonates for known G6PD mutations using established PCR‐based techniques. We found 50.0% (19 of 38) were mutation 1376G>T, 34.2% (13 of 38) were mutation 1388G>A, 5.2% (2 of 38 ) were mutation 95A>G and 2.2% (1 of 38) was mutation 1024C>T. In 7% (3 of 38) of the cases the mutations remained uncharacterised. Sixty three percent (24 of 38) of the G6PD deficient neonates had neonatal jaundice with 28.9 % (11 of 38) developing moderate to severe hyperbilirubinemia . The group of neonates with 1388 mutation showed the highest incidence of moderate to severe hyperbilirubinemia requiring phototherapy and/or exchange transfusion respectively. Majority (70%) of the G6PD deficient neonates showed severe enzyme deficiency. However, there was no meaningful association between the level of enzyme activity and the severity of neonatal jaundice. In summary, four mutations account for more than 90% of the G6PD deficiency cases among the Chinese in Malaysia and the pattern of distribution of the molecular variants is similar to those found among the Chinese in Taiwan and southern mainland China. Our findings also suggest the possible association of nt 1388 mutation with severe neonatal jaundice. Hum Mutat 14:352, 1999. © 1999 Wiley‐Liss, Inc.