Associated Regional and University Pathologists, Inc., ARUP Laboratories and University of Utah, Salt Lake City, UT 84132-2408, USA.
Blood Cells Mol Dis. 2012 Apr 15;48(4):203-8. doi: 10.1016/j.bcmd.2012.01.007. Epub 2012 Feb 22.
The G6PD c.563 C>T deficient mutation is endemic among Mediterranean populations but its clinical significance is not well delineated. We set up to estimate the proportion of G6PD deficient children presenting with hemolytic anemia at Al Nasser Pediatric Hospital at Gaza Strip, Palestine. We then established the prevalence of c.563T Mediterranean mutation and its linkage to c.1311 C>T polymorphism in this population.
G6PD deficiency was identified in children presenting with hemolytic anemia at Al Nasser Pediatric Hospital by spectrophotometric measurement of G6PD activity. G6PD exon 6 and exon 11 were amplified from genomic DNA and evaluated for c.563T mutation by sequencing and the c.1311T polymorphism by restriction fragment analysis. Seventy X-chromosomes (60 males and 5 females) from G6PD deficient patients and 40 X-chromosomes from a control group known to be not G6PD deficient were tested.
Over 80% of these children presenting with hemolytic anemia were G6PD deficient and 34% of these had the Mediterranean G6PD deficient variant. The allelic frequencies of Mediterranean c.563T and c.1311T polymorphisms among G6PD deficient patients were 0.33 and 0.38 respectively. The c.1311T polymorphism was linked in 95.2% of patients with the Mediterranean mutation, an allele frequency of 0.87, compared to the control non-G6PD deficient group with an allele frequency of 0.18.
We conclude that G6PD deficiency accounts for majority of hemolytic anemia encountered in Gaza children treated at Al Nasser Pediatric Hospital Emergency department. The Mediterranean mutation c.563T, while not accounting for a majority of G6PD deficiency, is common among G6PD deficient Gaza Strip Palestinians and is frequently, but not always, linked to the c.1311T polymorphism. This work provides a foundation for the population screening of Palestinians for G6PD deficiency and for investigations of ancestral origin of the Mediterranean variant in world populations.
G6PD c.563 C>T 缺陷突变在地中海人群中流行，但临床意义尚不清楚。我们旨在估计在巴勒斯坦加沙地带的 Al Nasser 儿科医院就诊的患有溶血性贫血的 G6PD 缺乏儿童的比例。然后，我们确定了该人群中 c.563T 地中海突变及其与 c.1311 C>T 多态性的相关性。
通过分光光度法测定 G6PD 活性，在 Al Nasser 儿科医院就诊的患有溶血性贫血的儿童中确定 G6PD 缺乏症。从基因组 DNA 扩增 G6PD 外显子 6 和外显子 11，并通过测序评估 c.563T 突变，通过限制性片段分析评估 c.1311T 多态性。对 70 条来自 G6PD 缺乏症患者的 X 染色体（60 条男性和 5 条女性）和 40 条来自已知非 G6PD 缺乏症的对照组的 X 染色体进行检测。
这些患有溶血性贫血的儿童中，超过 80%的儿童患有 G6PD 缺乏症，其中 34%的儿童存在地中海 G6PD 缺乏变异。地中海 c.563T 和 c.1311T 多态性的等位基因频率分别为 0.33 和 0.38。在患有地中海突变的患者中，c.1311T 多态性的连锁频率为 95.2%，等位基因频率为 0.87，而对照组中非 G6PD 缺乏症患者的等位基因频率为 0.18。
我们得出结论，G6PD 缺乏症是加沙儿童在 Al Nasser 儿科医院急诊室就诊时遇到的大多数溶血性贫血的原因。地中海突变 c.563T 虽然没有占到 G6PD 缺乏症的多数，但在加沙地带的巴勒斯坦人中很常见，并且经常（但并非总是）与 c.1311T 多态性相关。这项工作为巴勒斯坦人进行 G6PD 缺乏症的人群筛查以及研究世界人群中地中海变异的祖先起源提供了基础。
