Haishen Tang, Yi Xiong, Jiaqi Tang, Xiaohong Wang, Ya Wang, Liping Huang, Runli Wang, Degang Wang
{"title":"罕见地中海贫血变异基因的筛查和诊断。","authors":"Haishen Tang, Yi Xiong, Jiaqi Tang, Xiaohong Wang, Ya Wang, Liping Huang, Runli Wang, Degang Wang","doi":"10.5858/arpa.2023-0382-OA","DOIUrl":null,"url":null,"abstract":"CONTEXT.—\nRare thalassemia subtypes are often undiagnosed because conventional testing methods can only identify 23 common types of α- and β-thalassemia.\n\n\nOBJECTIVE.—\nTo assess a comprehensive approach for the screening and diagnosis of rare thalassemia.\n\n\nDESIGN.—\nThe study cohort included 72 individuals with suspected rare thalassemia variants. Screening was conducted by next-generation sequencing (NGS) combined with third-generation sequencing (TGS) and chromosomal microarray analysis (CMA)/copy number variation sequencing.\n\n\nRESULTS.—\nOf the 72 individuals with suspected rare thalassemia, 49 had rare α- or β-gene variants. NGS combined with gap polymerase chain reaction detected a total of 42 cases, resulting in a positive detection rate of 58.3%. Additionally, 4 α-globin genetic deletions were identified by TGS, which increased the variant detection rate by 5.6%. Two samples with a microdeletion of chromosome 16 or 11 were detected by CMA, which increased the detection rate by 2.8%. For one sample, reanalysis of the NGS and TGS data confirmed the presence of the β41-42/βN and βN/βN mosaic. The HBB:c.315 + 2delT mutation was initially reported in Guangdong Province, China. Two HBB gene mutations (HBB:c.315 + 5G>C and HBB:c.295G>A) and 4 rare HBA gene deletions (-11.1, -α27.6, -α2.4, and -α21.9) were initially identified in the Zhonshan region. The hematologic phenotypes of all rare cases in this study were clarified.\n\n\nCONCLUSIONS.—\nRare thalassemia variants are more common than previously thought. Despite advancements in TGS, there is still no foolproof method for detection of all types of thalassemia. Thus, a comprehensive approach is necessary for accurate screening and diagnosis of rare thalassemia variants.","PeriodicalId":3,"journal":{"name":"ACS Applied Electronic Materials","volume":"33 27","pages":""},"PeriodicalIF":4.3000,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Screening and Diagnosis of Rare Thalassemia Variants.\",\"authors\":\"Haishen Tang, Yi Xiong, Jiaqi Tang, Xiaohong Wang, Ya Wang, Liping Huang, Runli Wang, Degang Wang\",\"doi\":\"10.5858/arpa.2023-0382-OA\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"CONTEXT.—\\nRare thalassemia subtypes are often undiagnosed because conventional testing methods can only identify 23 common types of α- and β-thalassemia.\\n\\n\\nOBJECTIVE.—\\nTo assess a comprehensive approach for the screening and diagnosis of rare thalassemia.\\n\\n\\nDESIGN.—\\nThe study cohort included 72 individuals with suspected rare thalassemia variants. Screening was conducted by next-generation sequencing (NGS) combined with third-generation sequencing (TGS) and chromosomal microarray analysis (CMA)/copy number variation sequencing.\\n\\n\\nRESULTS.—\\nOf the 72 individuals with suspected rare thalassemia, 49 had rare α- or β-gene variants. NGS combined with gap polymerase chain reaction detected a total of 42 cases, resulting in a positive detection rate of 58.3%. Additionally, 4 α-globin genetic deletions were identified by TGS, which increased the variant detection rate by 5.6%. Two samples with a microdeletion of chromosome 16 or 11 were detected by CMA, which increased the detection rate by 2.8%. For one sample, reanalysis of the NGS and TGS data confirmed the presence of the β41-42/βN and βN/βN mosaic. The HBB:c.315 + 2delT mutation was initially reported in Guangdong Province, China. Two HBB gene mutations (HBB:c.315 + 5G>C and HBB:c.295G>A) and 4 rare HBA gene deletions (-11.1, -α27.6, -α2.4, and -α21.9) were initially identified in the Zhonshan region. The hematologic phenotypes of all rare cases in this study were clarified.\\n\\n\\nCONCLUSIONS.—\\nRare thalassemia variants are more common than previously thought. Despite advancements in TGS, there is still no foolproof method for detection of all types of thalassemia. 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Screening and Diagnosis of Rare Thalassemia Variants.
CONTEXT.—
Rare thalassemia subtypes are often undiagnosed because conventional testing methods can only identify 23 common types of α- and β-thalassemia.
OBJECTIVE.—
To assess a comprehensive approach for the screening and diagnosis of rare thalassemia.
DESIGN.—
The study cohort included 72 individuals with suspected rare thalassemia variants. Screening was conducted by next-generation sequencing (NGS) combined with third-generation sequencing (TGS) and chromosomal microarray analysis (CMA)/copy number variation sequencing.
RESULTS.—
Of the 72 individuals with suspected rare thalassemia, 49 had rare α- or β-gene variants. NGS combined with gap polymerase chain reaction detected a total of 42 cases, resulting in a positive detection rate of 58.3%. Additionally, 4 α-globin genetic deletions were identified by TGS, which increased the variant detection rate by 5.6%. Two samples with a microdeletion of chromosome 16 or 11 were detected by CMA, which increased the detection rate by 2.8%. For one sample, reanalysis of the NGS and TGS data confirmed the presence of the β41-42/βN and βN/βN mosaic. The HBB:c.315 + 2delT mutation was initially reported in Guangdong Province, China. Two HBB gene mutations (HBB:c.315 + 5G>C and HBB:c.295G>A) and 4 rare HBA gene deletions (-11.1, -α27.6, -α2.4, and -α21.9) were initially identified in the Zhonshan region. The hematologic phenotypes of all rare cases in this study were clarified.
CONCLUSIONS.—
Rare thalassemia variants are more common than previously thought. Despite advancements in TGS, there is still no foolproof method for detection of all types of thalassemia. Thus, a comprehensive approach is necessary for accurate screening and diagnosis of rare thalassemia variants.
期刊介绍:
ACS Applied Electronic Materials is an interdisciplinary journal publishing original research covering all aspects of electronic materials. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrate knowledge in the areas of materials science, engineering, optics, physics, and chemistry into important applications of electronic materials. Sample research topics that span the journal's scope are inorganic, organic, ionic and polymeric materials with properties that include conducting, semiconducting, superconducting, insulating, dielectric, magnetic, optoelectronic, piezoelectric, ferroelectric and thermoelectric.
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