{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T01:45:31Z","timestamp":1793324731753,"version":"4.5.0"},"reference-count":29,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T00:00:00Z","timestamp":1729555200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Science and Technology Projects in Guangzhou","award":["202201020618"],"award-info":[{"award-number":["202201020618"]}]},{"name":"Scientific research Project plan of Shanghai Municipal Health Commission","award":["202140346"],"award-info":[{"award-number":["202140346"]}]},{"name":"Application Technology Research and Development Project of Inner Mongolia Autonomous Region","award":["2020GG0119"],"award-info":[{"award-number":["2020GG0119"]}]},{"name":"Open Fund of Yunnan Provincial Key Laboratory for Birth Defects and Genetic Diseases","award":["2020ZDKFKT001"],"award-info":[{"award-number":["2020ZDKFKT001"]}]},{"name":"Open Fund of Reproductive Obstetrics and Gynecology Clinical Center of Yunnan Province","award":["2022LCZXKF-SZ02"],"award-info":[{"award-number":["2022LCZXKF-SZ02"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background and aims<\/jats:title>\n                    <jats:p>Newborn screening (NBS) for glucose-6-phosphate dehydrogenase (G6PD) deficiency by biochemical tests is being used worldwide, however, the outcomes arising from combined genetic and biochemical tests have not been evaluated. This research aimed to evaluate the outcomes of application of combined genetic and biochemical NBS for G6PD deficiency and to investigate the molecular epidemiological characteristics, variant spectrum, and genotype-phenotype correlation of G6PD deficiency in China.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A population-based cohort of 29,601 newborns were prospectively recruited from eight NBS centers in China between February 21 and December 30, 2021. Biochemical and genetic NBS was conducted simultaneously.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The overall prevalence of G6PD deficiency was 1.12% (1.86% for male, and 0.33% for female; 1.94% for South China and 0.08% for North China). Genetic NBS identified 10 male patients undetected by biochemical NBS. The overall positive predictive values (PPVs) of biochemical and genetic NBS were 79.95% and 47.57%, respectively. A total of 15 variants were identified, with the six most common variants being c.1388G &gt; A, c.1376G &gt; T, c.95A &gt; G, c.871G &gt; A, c.1024C &gt; T and c.392G &gt; T (94.2%). The activity of G6PD was correlated with the type and WHO classification of variants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study highlighted that combined screening could enhance the efficiency of current NBS for diagnosing G6PD deficiency. The prevalence, variant spectrum and allele frequency of G6PD deficiency vary across different regions. Our data provide valuable references for clinical practice and optimization of future screening strategies for G6PD deficiency.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0310517","type":"journal-article","created":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T13:33:58Z","timestamp":1729604038000},"page":"e0310517","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["Molecular epidemiological characteristics, variant spectrum and genotype-phenotype correlation of glucose-6-phosphate dehydrogenase deficiency in China: A population-based multicenter study using newborn screening"],"prefix":"10.1371","volume":"19","author":[{"given":"Minyi","family":"Tan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiulian","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinhong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulu","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunjing","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengfang","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyun","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunna","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohua","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jizhen","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianshu","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingkun","family":"Miao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5991-1752","authenticated-orcid":true,"given":"Baosheng","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cidan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7527-3754","authenticated-orcid":true,"given":"Yonglan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,10,22]]},"reference":[{"key":"pone.0310517.ref001","doi-asserted-by":"crossref","first-page":"875877","DOI":"10.3389\/fped.2022.875877","article-title":"Glucose-6-Phosphate Dehydrogenase Deficiency and Neonatal Hyperbilirubinemia: Insights on Pathophysiology, Diagnosis, and Gene Variants in Disease Heterogeneity[J].","volume":"10","author":"Y Lee H","year":"2022","journal-title":"Front Pediatr,"},{"issue":"9606","key":"pone.0310517.ref002","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/S0140-6736(08)60073-2","article-title":"Glucose-6-phosphate dehydrogenase deficiency[J]","volume":"371","author":"D Cappellini M","year":"2008","journal-title":"Lancet"},{"issue":"5","key":"pone.0310517.ref003","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1007\/s00439-005-0126-5","article-title":"Structure and function of glucose-6-phosphate dehydrogenase-deficient variants in Chinese population[J].","volume":"119","author":"W Jiang","year":"2006","journal-title":"Hum Genet"},{"issue":"1","key":"pone.0310517.ref004","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1002\/humu.23911","article-title":"Chinese newborn screening for the incidence of G6PD deficiency and variant of G6PD gene from 2013 to 2017[J].","volume":"41","author":"Z Liu","year":"2020","journal-title":"Hum Mutat"},{"issue":"8","key":"pone.0310517.ref005","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.1002\/j.1460-2075.1986.tb04436.x","article-title":"Structural analysis of the X-linked gene encoding human glucose 6-phosphate dehydrogenase[J]","volume":"5","author":"G Martini","year":"1986","journal-title":"EMBO J"},{"issue":"1","key":"pone.0310517.ref006","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1056\/NEJMra1708111","article-title":"Favism and Glucose-6-Phosphate Dehydrogenase Deficiency[J]","volume":"378","author":"L Luzzatto","year":"2018","journal-title":"N Engl J Med"},{"issue":"1","key":"pone.0310517.ref007","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1111\/bjh.16366","article-title":"Laboratory diagnosis of G6PD deficiency. A British Society for Haematology Guideline[J]","volume":"189","author":"D Roper","year":"2020","journal-title":"Br J Haematol"},{"issue":"6","key":"pone.0310517.ref008","first-page":"601","article-title":"WHO Working Group[J].","volume":"67","author":"Glucose-6-phosphate dehydrogenase deficiency","year":"1989","journal-title":"Bull World Health Organ"},{"issue":"3","key":"pone.0310517.ref009","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1053\/j.semperi.2011.02.010","article-title":"Neonatal screening for glucose-6-phosphate dehydrogenase deficiency: biochemical versus genetic technologies[J].","volume":"35","author":"M Kaplan","year":"2011","journal-title":"Semin Perinatol"},{"issue":"6","key":"pone.0310517.ref010","first-page":"411","article-title":"[Consensus statement on neonatal screening, diagnosis and treatment for glucose-6-phosphate dehydrogenase deficiency][J].","volume":"55","year":"2017","journal-title":"Zhonghua Er Ke Za Zhi"},{"issue":"11","key":"pone.0310517.ref011","first-page":"1275","article-title":"[Correlation analysis of genotypes and the enzymatic activities of glucose-6-phosphate dehydrogenase in neonates in Guangzhou][J].","volume":"54","author":"F Tang","year":"2020","journal-title":"Zhonghua Yu Fang Yi Xue Za Zhi"},{"issue":"11","key":"pone.0310517.ref012","doi-asserted-by":"crossref","first-page":"2683","DOI":"10.1007\/s00277-021-04630-9","article-title":"Epidemiological shift of glucose-6-phosphate dehydrogenase mutations in northern Italy in the last 15 years[J]","volume":"100","author":"L Duca","year":"2021","journal-title":"Ann Hematol"},{"issue":"1","key":"pone.0310517.ref013","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s12863-018-0664-1","article-title":"High resolution melting curve analysis enables rapid and reliable detection of G6PD variants in heterozygous females[J]","volume":"19","author":"T Islam M","year":"2018","journal-title":"BMC Genet"},{"key":"pone.0310517.ref014","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.cca.2019.04.074","article-title":"Applying a multiplexed primer extension method on dried blood spots increased the detection of carriers at risk of glucose-6-phosphate dehydrogenase deficiency in newborn screening program[J]","volume":"495","author":"H Chiu Y","year":"2019","journal-title":"Clin Chim Acta"},{"issue":"2","key":"pone.0310517.ref015","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1159\/000489009","article-title":"Prevalence and Molecular Study of G6PD Deficiency in the Dai and Jingpo Ethni Groups in the Dehong Prefecture of the Yunnan Province[J]","volume":"83","author":"M He","year":"2018","journal-title":"Hum Hered"},{"issue":"17","key":"pone.0310517.ref016","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.21037\/atm-20-1147","article-title":"A pilot study of expanded newborn screening for 573 genes related to severe inherited disorders in China: results from 1,127 newborns[J].","volume":"8","author":"X Luo","year":"2020","journal-title":"Ann Transl Med"},{"issue":"1","key":"pone.0310517.ref017","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1186\/s13023-021-02116-5","article-title":"NeoSeq: a new method of genomic sequencing for newborn screening[J].","volume":"16","author":"H Wang","year":"2021","journal-title":"Orphanet J Rare Dis"},{"issue":"1","key":"pone.0310517.ref018","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.jgg.2021.08.008","article-title":"Newborn screening with targeted sequencing: a multicenter investigation and a pilot clinical study in China[J]","volume":"49","author":"C Hao","year":"2022","journal-title":"J Genet Genomics"},{"key":"pone.0310517.ref019","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.cca.2022.01.015","article-title":"Combined genetic screening and traditional biochemical screening to optimize newborn screening systems[J]","volume":"528","author":"X Wang","year":"2022","journal-title":"Clin Chim Acta"},{"issue":"1","key":"pone.0310517.ref020","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/s13023-022-02231-x","article-title":"Application of a next-generation sequencing (NGS) panel in newborn screening efficiently identifies inborn disorders of neonates[J].","volume":"17","author":"X Huang","year":"2022","journal-title":"Orphanet J Rare Dis"},{"issue":"6","key":"pone.0310517.ref021","doi-asserted-by":"crossref","first-page":"e843","DOI":"10.1002\/ctm2.843","article-title":"A pilot study of assessing whole genome sequencing in newborn screening in unselected children in China[J].","volume":"12","author":"M Jian","year":"2022","journal-title":"Clin Transl Med"},{"issue":"9","key":"pone.0310517.ref022","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1038\/s41591-020-0966-5","article-title":"The role of exome sequencing in newborn screening for inborn errors of metabolism[J]","volume":"26","author":"N Adhikari A","year":"2020","journal-title":"Nat Med"},{"issue":"9","key":"pone.0310517.ref023","doi-asserted-by":"crossref","first-page":"e2331162","DOI":"10.1001\/jamanetworkopen.2023.31162","article-title":"Genomic Sequencing as a First-Tier Screening Test and Outcomes of Newborn Screening[J]","volume":"6","author":"T Chen","year":"2023","journal-title":"JAMA Netw Open"},{"issue":"5","key":"pone.0310517.ref024","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology[J]","volume":"17","author":"S Richards","year":"2015","journal-title":"Genet Med"},{"key":"pone.0310517.ref025","doi-asserted-by":"crossref","first-page":"104597","DOI":"10.1016\/j.meegid.2020.104597","article-title":"Prevalence and spectrum of mutations causing G6PD deficiency in Indian populations[J]","volume":"86","author":"R Devendra","year":"2020","journal-title":"Infect Genet Evol"},{"issue":"1","key":"pone.0310517.ref026","doi-asserted-by":"crossref","first-page":"17106","DOI":"10.1038\/s41598-020-74200-y","article-title":"Glucose-6-phosphate dehydrogenase deficiency in the Han Chinese population: molecular characterization and genotype-phenotype association throughout an activity distribution[J].","volume":"10","author":"Y He","year":"2020","journal-title":"Sci Rep"},{"key":"pone.0310517.ref027","doi-asserted-by":"crossref","first-page":"718503","DOI":"10.3389\/fgene.2021.718503","article-title":"Newborn Screening for G6PD Deficiency in Xiamen, China: Prevalence, Variant Spectrum, and Genotype-Phenotype Correlations[J].","volume":"12","author":"X Wang","year":"2021","journal-title":"Front Genet"},{"key":"pone.0310517.ref028","first-page":"2653089","article-title":"Molecular Characterization and Genotype-Phenotype Correlation of G6PD Mutations in Five Ethnicities of Northern Vietnam[J].","volume":"2022","author":"T Ngo T","year":"2022","journal-title":"Anemia"},{"issue":"1","key":"pone.0310517.ref029","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s40246-023-00473-9","article-title":"Genotypic and phenotypic characterization of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Guangzhou, China[J].","volume":"17","author":"Z Li","year":"2023","journal-title":"Hum Genomics"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0310517","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T13:34:14Z","timestamp":1729604054000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0310517"}},"subtitle":[],"editor":[{"given":"Elizabeth S.","family":"Mayne","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,10,22]]},"references-count":29,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,10,22]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0310517","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,22]]}}}