Simultaneous detection of G6PD mutations using SNPscan in a multiethnic minority area of Southwestern China

Wei, Huagui; Wang, Chunfang; Huang, Weixin; He, Lei; Huang, Huiying; Chen, Wen‐Cheng; Zheng, Yuzhong; Xu, Guidan; Lin, Liyun; Wei, Wujun; Chen, Weizhong; Chen, Liying; Wang, Junli; Lin, Min

doi:10.3389/fgene.2022.1000290

Cited by 4 publications

(2 citation statements)

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“…Heterozygous c.519C>T mutation was detected in a subject presenting intermediate G6PD activity (8.14 U/gHb; 68.23% of the AMM). The c.519C>T is a rare mutation that has previously been reported in Chinese, Taiwanese, and Thai populations [34][35][36]. The mutation…”

Section: Plos Onementioning

confidence: 92%

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: 92%

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 pediatrics, however, severe hemolysis hyperbilirubinemia and jaundice due to G6PD deficiency in newborns can lead to hearing deficits, behavior disorders, and long-lasting neurologic damage [14]. G6PD mutations are common among geographically defined populations, including those originating in the Mediterranean Basin and other parts of the Middle East [15], and some East Asian [16] and African populations. The metabolic changes linked to G6PD deficiency may result in an elevated production of reactive oxygen species (ROS) and an imbalance in the antioxidant system [11,17], setting off a molecular cascade resulting in impaired astrocyte function, neuron death [18], and damage to DNA.…”

Section: Introductionmentioning

confidence: 99%

The Association between Glucose 6-Phosphate Dehydrogenase Deficiency and Attention Deficit/Hyperactivity Disorder

Merzon,

Magen,

Ashkenazi

et al. 2023

Nutrients

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Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency, impacting 4.9% of the population and more prevalent in Mediterranean communities, is a common enzymopathy with potential relevance to Attention Deficit/Hyperactivity Disorder (ADHD). This study investigated this association. Methods: The clinical characteristics of 7473 G6PD-deficient patients and 29,892 matched case–controls (selected at a 1:4 ratio) from a cohort of 1,031,354 within the Leumit Health Services database were analyzed using Fisher’s exact test for categorical variables and the Mann–Whitney U test for continuous variables. Results: In total, 68.7% were male. The mean duration of follow-up was 14.3 ± 6.2 years at a mean age of 29.2 ± 22.3 years. G6PD deficiency was associated with an increased risk of being diagnosed with ADHD (Odds Ratio (OR) = 1.16 [95% CI, 1.08–1.25], p < 0.001), seeking care from adult neurologists (OR = 1.30 [95% CI, 1.22–1.38], p < 0.001), and consulting adult psychiatrists (OR = 1.12 [95% CI, 1.01–1.24], p = 0.048). The use of stimulant medications among G6PD-deficient individuals was 17% higher for the methylphenidate class of drugs (OR = 1.17 [95% CI, 1.08, 1.27], p < 0.001), and there was a 16% elevated risk for amphetamine use (OR = 1.16 [95% CI, 1.03, 1.37], p = 0.047). Conclusions: G6PD deficiency signals an increased risk of ADHD diagnosis, more severe presentations of ADHD and a greater need for psychiatric medications to treat ADHD.

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SNPscan Combined With CNVplex as a High‐Performance Diagnostic Method for Thalassemia

Wei,

Wang,

Xiong

et al. 2024

Prenatal Diagnosis

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ObjectiveThalassemia is a Mendelian‐inherited blood disorder with severe consequences, including disability and mortality, making it a significant public health concern. Therefore, there is an urgent need for precise diagnostic technologies. We introduce two innovative diagnostic techniques for thalassemia, SNPscan and CNVplex, designed to enhance molecular diagnostics of thalassemia.MethodsThe SNPscan and CNVplex assays utilize variations in PCR product length and fluorescence to identify multiple mutations. In the SNPscan method, we designed three probes per locus: two 5′ and one 3′, and incorporated allele identification link sequences into one of the 5′ probes to distinguish the alleles. The detection system was designed for 67 previously reported loci in the Chinese population for a specific genetic condition. CNVplex identifies deletion types by analyzing the specific positions of probes within the globin gene. This innovative approach enables the detection of six distinct deletional mutations, enhancing the precision of thalassemia diagnostics. We evaluated and refined the methodologies in a training cohort of 100 individuals with confirmed HBA and HBB genotypes. The validation cohort, consisting of 1647 thalassemia patients and 100 healthy controls, underwent a double‐blind study. Traditional diagnostic techniques served as the control methods.ResultsIn the training set of 100 samples, 10 mutations (Hb QS, Hb CS, Hb Westmead, CD17, CD26, CD41‐42, IVS‐II‐654, ‐‐SEA, −α3.7 and −α4.2) were identified, consistent with those identified by traditional methods. The validation study showed that SNPscan/CNVplex offered superior molecular diagnostic capabilities for thalassemia, with 100% accuracy compared to 99.43% for traditional methods. Notably, the assay identified three previously undetected mutations in 10 cases, including two deletion mutations (Chinese Gγ(Aγδβ)0 del and SEA‐HPFH), and one non‐deletion mutation (Hb Q‐Thailand).ConclusionsThe SNPscan/CNVplex assay is a cost‐effective and user‐friendly tool for diagnosing thalassemia, demonstrating high accuracy and reliability, and showing great potential as a primary diagnostic method in clinical practice.

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Simultaneous detection of G6PD mutations using SNPscan in a multiethnic minority area of Southwestern China

Cited by 4 publications

References 50 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

The Association between Glucose 6-Phosphate Dehydrogenase Deficiency and Attention Deficit/Hyperactivity Disorder

SNPscan Combined With CNVplex as a High‐Performance Diagnostic Method for Thalassemia

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