{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T10:08:30Z","timestamp":1782382110331,"version":"3.54.5"},"reference-count":78,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T00:00:00Z","timestamp":1700006400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016175","name":"Chulabhorn Royal Academy","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016175","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Mahidol University (Fundamental Fund: fiscal year 2023 by National Science Research and Innovation Fund"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked enzymopathy caused by mutations in the <jats:italic>G6PD<\/jats:italic> 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 <jats:italic>G6PD<\/jats:italic> mutations, especially among females with heterozygous deficiency. Multiplex HRM assays were developed to detect six <jats:italic>G6PD<\/jats:italic> variants, i.e., <jats:italic>G6PD<\/jats:italic> Gaohe (c.95A&gt;G), <jats:italic>G6PD<\/jats:italic> Chinese-4 (c.392G&gt;T), <jats:italic>G6PD<\/jats:italic> Mahidol (c.487G&gt;A), <jats:italic>G6PD<\/jats:italic> Viangchan (c.871G&gt;A), <jats:italic>G6PD<\/jats:italic> Chinese-5 (c.1024C&gt;T), and <jats:italic>G6PD<\/jats:italic> Union (c.1360C&gt;T) in two reactions. The assays were validated and then applied to genotype <jats:italic>G6PD<\/jats:italic> mutations in 248 Thai females. The sensitivity of the HRM assays developed was 100% [95% confidence interval (CI): 94.40%\u2013100%] with a specificity of 100% (95% CI: 88.78%\u2013100%) 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 <jats:italic>G6PD<\/jats:italic> Viangchan. Interestingly, a deletion in intron 5 nucleotide position 637\/638 (c.486-34delT) was also detected by the developed HRM assays. <jats:italic>G6PD<\/jats:italic> genotyping revealed a total of 12 <jats:italic>G6PD<\/jats:italic> genotypes, with a high prevalence of intronic variants. Our results suggested that HRM analysis-based genotyping is a simple and reliable approach for detecting <jats:italic>G6PD<\/jats:italic> 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 <jats:italic>G6PD<\/jats:italic> expression and contribute to enzyme deficiency.<\/jats:p>","DOI":"10.1371\/journal.pone.0294200","type":"journal-article","created":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T18:37:12Z","timestamp":1700073432000},"page":"e0294200","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Molecular characterization of G6PD mutations identifies new mutations and a high frequency of intronic variants in Thai females"],"prefix":"10.1371","volume":"18","author":[{"given":"Kamonwan","family":"Chamchoy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sirapapha","family":"Sudsumrit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jutamas","family":"Wongwigkan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songsak","family":"Petmitr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duantida","family":"Songdej","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily 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