Molecular heterogeneity of glucose-6-phosphate dehydrogenase deficiency in neonates in Wuhan: Description of four novel variants

Shen, Songdong; Xiong, Qian; Cai, Wenqian; Hu, Rui; Zhou, Bin; Hu, Xi‐Jiang

doi:10.3389/fgene.2022.994015

Cited by 7 publications

(6 citation statements)

References 24 publications

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“…This deletion was previously reported as a sporadic variant in the Chinese population [54,[60][61][62]. In a study in Wuhan, c.486-34delT was found at a rate of 2% among G6PD variants, which was associated with an enzyme activity of 2.37 U/gHb [60]. Although the effect of this mutation on the expression of the G6PD gene has not been described, the c.486-34delT was found to be associated with reduced G6PD activity in the studied population.…”

Section: Plos Onementioning

confidence: 59%

“…The average G6PD activity in individuals carrying this variant was 7.11 ± 1.72 U/gHb (59.60% of the AMM). This deletion was previously reported as a sporadic variant in the Chinese population [54,[60][61][62]. In a study in Wuhan, c.486-34delT was found at a rate of 2% among G6PD variants, which was associated with an enzyme activity of 2.37 U/gHb [60].…”

Section: Plos Onementioning

confidence: 68%

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

Chamchoy,

Sudsumrit,

Wongwigkan

et al. 2023

PLoS ONE

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Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked enzymopathy caused by mutations in the G6PD gene. A medical concern associated with G6PD deficiency is acute hemolytic anemia induced by certain foods, drugs, and infections. Although phenotypic tests can correctly identify hemizygous males, as well as homozygous and compound heterozygous females, heterozygous females with a wide range of G6PD activity may be misclassified as normal. This study aimed to develop multiplex high-resolution melting (HRM) analyses to enable the accurate detection of G6PD mutations, especially among females with heterozygous deficiency. Multiplex HRM assays were developed to detect six G6PD variants, i.e., G6PD Gaohe (c.95A>G), G6PD Chinese-4 (c.392G>T), G6PD Mahidol (c.487G>A), G6PD Viangchan (c.871G>A), G6PD Chinese-5 (c.1024C>T), and G6PD Union (c.1360C>T) in two reactions. The assays were validated and then applied to genotype G6PD mutations in 248 Thai females. The sensitivity of the HRM assays developed was 100% [95% confidence interval (CI): 94.40%–100%] with a specificity of 100% (95% CI: 88.78%–100%) for detecting these six mutations. The prevalence of G6PD deficiency was estimated as 3.63% (9/248) for G6PD deficiency and 31.05% (77/248) for intermediate deficiency by phenotypic assay. The developed HRM assays identified three participants with normal enzyme activity as heterozygous for G6PD Viangchan. Interestingly, a deletion in intron 5 nucleotide position 637/638 (c.486-34delT) was also detected by the developed HRM assays. G6PD genotyping revealed a total of 12 G6PD genotypes, with a high prevalence of intronic variants. Our results suggested that HRM analysis-based genotyping is a simple and reliable approach for detecting G6PD mutations, and could be used to prevent the misdiagnosis of heterozygous females by phenotypic assay. This study also sheds light on the possibility of overlooking intronic variants, which could affect G6PD expression and contribute to enzyme deficiency.

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Section: Plos Onementioning

confidence: 59%

Section: Plos Onementioning

confidence: 68%

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

Chamchoy,

Sudsumrit,

Wongwigkan

et al. 2023

PLoS ONE

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“…In addition to being used for the diagnosis of G6PD deficiency, genotyping of G6PD is also mainly used for epidemiological investigations and further exploration research on genotype-phenotype correlations. Except for a few rare small deletions, the G6PD gene mutations are almost all single nucleotide substitutions in the Chinese population ( Lin et al, 2018 ; Shen et al, 2022 ). Although the prevalence of G6PD mutations varies genetically among different regions and races, the 12 G6PD variants included in this study for genotyping of G6PD are the most prevalent in China.…”

Section: Discussionmentioning

confidence: 99%

Screening and the analysis of genotypic and phenotypic characterization of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Fujian province, China

Zhou,

Zeng,

Tang

et al. 2024

Front. Genet.

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IntroductionGlucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked hereditary disorder in southern China. However, the incidence rate of G6PD deficiency and the frequency of the most common G6PD gene variants vary widely. The purpose of this study was to investigate the prevalence, genotype, and phenotypic features of G6PD deficiency in neonates in Fujian province, southeastern China.MethodsThis retrospective cohort study enrolled 2,789,002 newborns (1,521,431 males and 1,267,571 females) based on the newborn screening program for G6PD deficiency in Fujian Province between January 2010 and December 2021.ResultsOf the 2,789,002 newborns enrolled, 26,437 cases were diagnosed (22,939 males and 3,498 females), and the estimated prevalence of G6PD deficiency in Fujian province was 0.95%. The prevalence was significantly higher among males (1.51%) than in females (0.28%) (p < 0.00001). Among the 3,198 patients with G6PD deficiency, 3,092 cases (2,145 males and 947 females) were detected to have G6PD gene variants. The top six prevalent genotypes identified represented 90.84% (2095/3,198) of the total and included c.1376G > T (44.93%), c.1388G > A (18.42%), c.1024C > T (9.32%), c.95A > G (8.69%), c.392G > T (5.25%), and c.871G > A (4.22%). The frequency of genotypes with c.1388G > A, c.1024C > T, and c.871G > A was higher in males in the Fujian province than in females, while the frequency of genotypes with c.1376G > T was lower. Furthermore, when comparing the enzyme activities of the top six prevalent genotypes, there were significant differences in the enzyme activities among the genotypes of male hemizygotes and female heterozygotes. According to the new classification of G6PD variants proposed by the World Health Organization (WHO), the variants with c.1376G > T, c.95A > G, and c.871G > A were recognized as Class A, while the c.392G > T, c.1388G > A, and c.1024C > T were recognized as Class B.DiscussionTo the best of our knowledge, this study is the first to systematically describe the overview of epidemiological characteristics of newborn G6PD deficiency in Fujian province, China, including the screening rate, incidence rate, and variant spectrum. Additionally, we elucidated the relationship between the distribution of enzyme activity with specific mutations and their WHO classification patterns. Our results could provide strategies for screening, diagnosis, and genetic counseling of G6PD deficiency in this area.

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“…A ratio of G6PD/6-phosphogluconate dehydrogenase 1.0 or less was considered a G6PD deficiency. [ 9 ]…”

Section: Methodsmentioning

confidence: 99%

Prevalence and association of early onset severe hyperbilirubinemia in newborn in the East China region: Retrospective medical record analyses

Gao,

Zhao,

Chen

et al. 2023

Medicine

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Research on the prevalence and association of hyperbilirubinemia is controversial because of different cultures, demographics, and clinical conditions. The etiology of hyperbilirubinemia is affected by the environment and other factors in the newborn. The World Health Organization recommended a 1-day hospital stay after uncomplicated delivery, jaundice assessment before discharge, and screening on 3rd and 7th days after birth for hyperbilirubinemia. However, the implementation of these recommendations is difficult in China. The objective of this study was to evaluate the prevalence and association of early onset severe hyperbilirubinemia in newborns in East China. Retrospective medical record analyses for 250 cesarean sections or vaginal deliveries, ≥2 kg body weight, and negative for Hepatitis B surface antigen by birth newborns were performed. A biochemical analyzer, quantitative assay, and quantitative polymerase chain reaction were used to evaluate total serum bilirubin, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and gene variant phenotyping, respectively. A total in 33 (13%) newborns were reported with early onset severe hyperbilirubinemia (according to the American Academy of Pediatrics, total serum bilirubin ≥ 342 μmol/L within 6 hours of birth). All newborns with severe hyperbilirubinemia were hospitalized and underwent phototherapy. The mothers of all newborns had a gestational age ≥ 35 weeks. Hospitalization included artificial feeding, and breastfeeding was rare (P < .0001). ABO incompatibility (“O” blood type for mother and either “A” or “AB” or “B” blood type for newborn, P = .0411), G6PD deficiency (G6PD/6-phosphogluconate dehydrogenase ≤ 1.0 in quantitative assay, P = .0422), Rh incompatibility (the mother’s blood type was Rh negative and newborn blood type was Rh positive, P = .0416), fewer genotype rs4149056 frequencies (P = .0452), higher genotype rs2306283 frequencies (P = .0461), and higher genotype rs1805173 frequencies (P = .0471) were independent parameter for early onset severe hyperbilirubinemia of newborns. The prevalence of early onset severe hyperbilirubinemia in Chinese newborns is 13% in the East China region. Blood incompatibility, G6PD deficiency, fewer genotype rs4149056 frequencies, higher genotype rs2306283 frequencies, and higher genotype rs1805173 frequencies were independent predictors of early onset severe hyperbilirubinemia among newborns in the East China region (Level of Evidence: IV; Technical Efficacy: Stage 5).

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Molecular heterogeneity of glucose-6-phosphate dehydrogenase deficiency in neonates in Wuhan: Description of four novel variants

Cited by 7 publications

References 24 publications

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

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

Screening and the analysis of genotypic and phenotypic characterization of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Fujian province, China

Prevalence and association of early onset severe hyperbilirubinemia in newborn in the East China region: Retrospective medical record analyses

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