Boonyawat Boonchai, Phetthong Tim, Suksumek Nithipun, Traivaree Chanchai
Division of Medical Genetics, Department of Pediatrics, Phramongkutklao Hospital and Phramongkutklao College of Medicine, Bangkok, Thailand.
Division of Neonatology, Department of Pediatrics, Phramongkutklao Hospital and Phramongkutklao College of Medicine, Bangkok, Thailand.
Anemia. 2021 Feb 9;2021:6680925. doi: 10.1155/2021/6680925. eCollection 2021.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common X-linked inherited erythroenzymopathy in Thailand. The clinical and hematological manifestations of G6PD deficiency are variable.
This study aimed to characterize the genotype-phenotype correlation of G6PD mutations in Thai pediatric patients who were followed-up in Phramongkutklao Hospital, a tertiary center in central Thailand. . A total of 102 children including 73 males (71.6%) and 29 females (28.4%) were included in our study. Mutation analysis was performed by direct DNA sequencing of all coding exons of the G6PD gene. Ninety-one patients (89.2%) were presented with neonatal hyperbilirubinemia and 11 patients (10.8%) were presented with acute hemolytic anemia beyond the neonatal period.
Molecular analysis of the G6PD gene in 102 G6PD-deficient Thai children identified 12 different mutations. G6PD Viangchan (871G > A) and G6PD Canton (1376G > T) were the first (46.2%) and the second (15.4%) most common identified mutations among both male and female G6PD-deficient individuals, respectively. All affected males were hemizygous for G6PD mutations and had an average G6PD level of 16.7 ± 11.5 (3-76) IU/ml.RBC. Majority of female patients (27 in 29, 93.1%) were heterozygous for G6PD mutations and had an average G6PD level of 133.6 ± 43.4 (9-195) IU/ml.RBC. Two female patients (6.9%) were either homozygous or compound heterozygous for the mutations and had G6PD level in the affected male range (35 and 10 IU/ml.RBC). Only 1 in 27 heterozygous females (3.7%) had G6PD level in the affected male range (9 IU/ml.RBC) which is possibly explained by nonrandom X-chromosome inactivation. The correlation of genotypes, G6PD levels, and clinical phenotypes was not demonstrated in our study in which all of the included G6PD-deficient patients were presented with neonatal hyperbilirubinemia and acute hemolytic anemia, since the genotype-phenotype correlation is normally demonstrated in chronic nonspherocytic hemolytic anemia (CNSHA) G6PD-deficient individuals.
This study characterizes the molecular heterogeneity of G6PD variants causing G6PD deficiency in Thai children. Our study demonstrated the efficiency of direct DNA sequencing which can identify 12 missense mutations in Thai children.
葡萄糖-6-磷酸脱氢酶（G6PD）缺乏症是泰国最常见的X连锁遗传性红细胞酶病。G6PD缺乏症的临床和血液学表现各不相同。
本研究旨在描述泰国中部三级中心佛统皇家医院随访的泰国儿科患者中G6PD突变的基因型-表型相关性。我们的研究共纳入102名儿童，其中男性73名（71.6%），女性29名（28.4%）。通过对G6PD基因所有编码外显子进行直接DNA测序进行突变分析。91名患者（89.2%）出现新生儿高胆红素血症，11名患者（10.8%）出现新生儿期后急性溶血性贫血。
对102名G6PD缺乏的泰国儿童的G6PD基因进行分子分析，确定了12种不同的突变。G6PD Viangchan（871G＞A）和G6PD Canton（1376G＞T）分别是男性和女性G6PD缺乏个体中最常见的第一（46.2%）和第二（15.4%）常见突变。所有受影响的男性G6PD突变为半合子，平均G6PD水平为16.7±11.5（3 - 76）IU/ml.RBC。大多数女性患者（29名中的27名，93.1%）G6PD突变为杂合子，平均G6PD水平为133.6±43.4（9 - 195）IU/ml.RBC。两名女性患者（6.9%）突变为纯合子或复合杂合子，G6PD水平处于受影响男性的范围内（35和10 IU/ml.RBC）。27名杂合子女性中只有1名（3.7%）G6PD水平处于受影响男性的范围内（9 IU/ml.RBC），这可能是非随机X染色体失活所致。在我们的研究中，未证明基因型、G6PD水平和临床表型之间的相关性，因为所有纳入的G6PD缺乏患者均出现新生儿高胆红素血症和急性溶血性贫血，而基因型-表型相关性通常在慢性非球形细胞溶血性贫血（CNSHA）G6PD缺乏个体中得到证实。
本研究描述了导致泰国儿童G6PD缺乏的G6PD变异体的分子异质性。我们的研究证明了直接DNA测序的有效性，该方法可在泰国儿童中鉴定出12种错义突变。
Zotero 插件