Genotype-Phenotype Correlation of G6PD Mutations among Central Thai Children with G6PD Deficiency

Abstract

Background. 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. Objective. 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. Material and Method. 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. Results. 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. Conclusion. 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.

Molecular characterization of G6PD mutations identifies new mutations and a high frequency of intronic variants in Thai females

“…Our study involving molecular analysis agrees well with previous studies in which G6PD Viangchan was found to be the most common variant in central Thailand [18,21,27,[45][46][47][48]. All 13 individuals carrying the c.871G>A mutation were found to have the combination of c.1311C>T in exon 11 and c.1365-13T>C in intron 11.…”

Molecular Characterization and Genotype-Phenotype Correlation of G6PD Mutations in Five Ethnicities of Northern Vietnam

“…In addition, the Canton and Kaiping variants are the most prevalent in South West China with 20% and 79.16%, respectively, found in 17.7% and 24.2% of our samples [ 43 ]. Likewise, in Thailand, Canton and Kaiping are observed in 15.4% and 14.4% of G6PD deficiency cases, respectively [ 5 ]. The G6PD Union, which was presented at 15.04% in this study, is determined at 100% in the Khomu population and 9.5% in Thailand [ 20 , 44 ].…”

“…On the other hand, G6PD Gaohe is also an important Chinese variant with an incidence rate ranging from 8.8% to 14.2% in different studies and was identified at about 7.08% in this study [45][46][47]. e Chinese variants including Orissa (0.88%), Quing Yan (3.54%), NanKang (0.29%), Taiwan-2 (0.29%), Chinese-5 (0.29%), and Coimbra Shunde (0.29%), and European variants such as Valladolid (0.59%) and Mediterranean (0.29%) were rarely detected in Northern Vietnam but were observed in several studies with various frequencies [5,18,29,[48][49][50][51]. Moreover, Silent variants are the most common polymorphism of G6PD gene and have a high rate of distribution among populations [18,21,29].…”

“…e lack of the G6PD enzyme can cause hemolytic and related disorders such as clinical acute hemolysis, neonatal jaundice, and congenital hemolytic anemia [2,3]. G6PD de ciency, also known as favism, is the most prevalent enzyme disorder and is found worldwide [4][5][6]. An estimated 400 million people were in uenced globally by G6PD, and an average of 4100 people died every year from 1990 to 2013 [7].…”

Cell and Gene Therapy for Anemia: Hematopoietic Stem Cells and Gene Editing

“…Through the use of gene sequencing and polymerase chain reaction, various mutations were revealed in children of Han Chinese ethnicity, such as c.202G>A (in exon 4), c.406C>T (in exon 5), c.487G>A and c.493A>G (in exon 6), c.697G>C (in exon 7), c.1311C>T (in exon 11), c.1376G>T and c.1388G>A (in exon 12), 1365-13T>C (in intron 11), and 493A>G (in intron 6) [93]. Molecular analysis through direct DNA sequencing of the G6PD gene in 102 Thai pediatric patients with G6PD deficiency revealed 12 missense mutations, namely G6PD Viangchan (871G>A), G6PD Canton (1376G>T), G6PD Kaiping (1388G>A), G6PD Mahidol (487G>A), G6PD Quing Yan (392G>T), G6PD Coimbra (592C>T), G6PD Union (1360C>T), G6PD Songklanagarind (196T>A), G6PD Valladolid (406C>T), G6PD Aures (143C>T), G6PD Chinese-5 (1024C>T), and G6PD Mediterranean (563C>T) [94].…”