Xiao-Li Cheng, Ting Yang, Liu Yang, Yi-Juan Xin, Mu He, Lin Zhu, Jia-Yun Liu
{"title":"[由 F12 基因的 p.Gly175Cys 和 p.Gly542Ser 复合杂合突变引起的遗传性凝血因子 XII 缺乏症的血统分析]。","authors":"Xiao-Li Cheng, Ting Yang, Liu Yang, Yi-Juan Xin, Mu He, Lin Zhu, Jia-Yun Liu","doi":"10.19746/j.cnki.issn.1009-2137.2024.03.033","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To analyze the clinical phenotype and gene mutation of a genetic coagulation factor XII (FXII) deficiency pedigree and explore the molecular pathogenesis.</p><p><strong>Methods: </strong>The activated partial thromboplastin time (APTT) and FXII activity (FXII:C) were detected by clotting method. The FXII antigen (FXII:Ag) was tested with ELISA. All exons and flanks of <i>F12</i> gene were determined by Sanger sequencing. ClustalX-2.1-win, PROVEAN and Swiss-Pdb Viewer software were used to analyze the conservatism of amino acids at the mutant site, forecast whether the mutant amino acids were harmful and confirm the influence of the mutation on protein structure.</p><p><strong>Results: </strong>The APTT of the proband prolonged to 71.3 s. The FXII:C and FXII:Ag were decreased to 5% and 6%, respectively. There were two heterozygous missense mutations c.580G>T and c.1681G>A detected in exon 7 and exon 14 of <i>F12</i> gene, resulting in p.Gly175Cys and p.Gly542Ser, severally. Proband's father carried the p.Gly175Cys heterozygous mutation, while mother, brother and daughter had the p.Gly542Ser heterozygous mutation. Software analysis showed that both Gly175 and Gly542 were conserved, the two mutations were harmful and when mutations had occurred, the corresponding sites affected the protein local structure.</p><p><strong>Conclusion: </strong>The p.Gly175Cys and p.Gly542Ser compound heterozygous mutations are the molecular pathogenesis of the hereditary coagulation FXII deficiency pedigree. The p.Gly175Cys mutation has been detected for the first time in the world.</p>","PeriodicalId":35777,"journal":{"name":"中国实验血液学杂志","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"[Pedigree Analysis of Hereditary Coagulation Factor XII Deficiency Caused by Compound Heterozygous Mutation p.Gly175Cys and p.Gly542Ser of <i>F12</i> Gene].\",\"authors\":\"Xiao-Li Cheng, Ting Yang, Liu Yang, Yi-Juan Xin, Mu He, Lin Zhu, Jia-Yun Liu\",\"doi\":\"10.19746/j.cnki.issn.1009-2137.2024.03.033\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>To analyze the clinical phenotype and gene mutation of a genetic coagulation factor XII (FXII) deficiency pedigree and explore the molecular pathogenesis.</p><p><strong>Methods: </strong>The activated partial thromboplastin time (APTT) and FXII activity (FXII:C) were detected by clotting method. The FXII antigen (FXII:Ag) was tested with ELISA. All exons and flanks of <i>F12</i> gene were determined by Sanger sequencing. ClustalX-2.1-win, PROVEAN and Swiss-Pdb Viewer software were used to analyze the conservatism of amino acids at the mutant site, forecast whether the mutant amino acids were harmful and confirm the influence of the mutation on protein structure.</p><p><strong>Results: </strong>The APTT of the proband prolonged to 71.3 s. The FXII:C and FXII:Ag were decreased to 5% and 6%, respectively. There were two heterozygous missense mutations c.580G>T and c.1681G>A detected in exon 7 and exon 14 of <i>F12</i> gene, resulting in p.Gly175Cys and p.Gly542Ser, severally. Proband's father carried the p.Gly175Cys heterozygous mutation, while mother, brother and daughter had the p.Gly542Ser heterozygous mutation. Software analysis showed that both Gly175 and Gly542 were conserved, the two mutations were harmful and when mutations had occurred, the corresponding sites affected the protein local structure.</p><p><strong>Conclusion: </strong>The p.Gly175Cys and p.Gly542Ser compound heterozygous mutations are the molecular pathogenesis of the hereditary coagulation FXII deficiency pedigree. The p.Gly175Cys mutation has been detected for the first time in the world.</p>\",\"PeriodicalId\":35777,\"journal\":{\"name\":\"中国实验血液学杂志\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"中国实验血液学杂志\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.19746/j.cnki.issn.1009-2137.2024.03.033\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"中国实验血液学杂志","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.19746/j.cnki.issn.1009-2137.2024.03.033","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"Medicine","Score":null,"Total":0}
[Pedigree Analysis of Hereditary Coagulation Factor XII Deficiency Caused by Compound Heterozygous Mutation p.Gly175Cys and p.Gly542Ser of F12 Gene].
Objective: To analyze the clinical phenotype and gene mutation of a genetic coagulation factor XII (FXII) deficiency pedigree and explore the molecular pathogenesis.
Methods: The activated partial thromboplastin time (APTT) and FXII activity (FXII:C) were detected by clotting method. The FXII antigen (FXII:Ag) was tested with ELISA. All exons and flanks of F12 gene were determined by Sanger sequencing. ClustalX-2.1-win, PROVEAN and Swiss-Pdb Viewer software were used to analyze the conservatism of amino acids at the mutant site, forecast whether the mutant amino acids were harmful and confirm the influence of the mutation on protein structure.
Results: The APTT of the proband prolonged to 71.3 s. The FXII:C and FXII:Ag were decreased to 5% and 6%, respectively. There were two heterozygous missense mutations c.580G>T and c.1681G>A detected in exon 7 and exon 14 of F12 gene, resulting in p.Gly175Cys and p.Gly542Ser, severally. Proband's father carried the p.Gly175Cys heterozygous mutation, while mother, brother and daughter had the p.Gly542Ser heterozygous mutation. Software analysis showed that both Gly175 and Gly542 were conserved, the two mutations were harmful and when mutations had occurred, the corresponding sites affected the protein local structure.
Conclusion: The p.Gly175Cys and p.Gly542Ser compound heterozygous mutations are the molecular pathogenesis of the hereditary coagulation FXII deficiency pedigree. The p.Gly175Cys mutation has been detected for the first time in the world.