A Novel 165 Kb Duplication Involving the α-Globin Gene Cluster Is Identified by Low-Pass Whole Genome Sequencing in a Chinese Thalassemia Intermedia Patient.
Xiaohong He, Peirun Tian, Lijuan Zhong, Shanshan Peng, Shiping Chen, Lei Pan, Yutao Du, Rui Zhang
{"title":"A Novel 165 Kb Duplication Involving the α-Globin Gene Cluster Is Identified by Low-Pass Whole Genome Sequencing in a Chinese Thalassemia Intermedia Patient.","authors":"Xiaohong He, Peirun Tian, Lijuan Zhong, Shanshan Peng, Shiping Chen, Lei Pan, Yutao Du, Rui Zhang","doi":"10.1080/03630269.2024.2346143","DOIUrl":null,"url":null,"abstract":"<p><p>Copy number variations (CNVs) involving the α-globin gene cluster can lead to an imbalance in the proportion of α- and β-globin chains and consequently cause clinical symptoms of β-thalassemia. In our case, a 6-year-old boy, clinically diagnosed with β thalassemia intermedia, was admitted for further genetic diagnosis with his family. Targeted sequencing and third generation sequencing (TGS) were used to detect the possible variants of the thalassemia genes. Low-pass whole genome sequencing (lpWGS) was conducted to specify the exact location of relevant CNVs across the genome, which was then validated by multiplex ligation-dependent probe amplification.The results revealed that the patient had a heterozygous β<sup>0</sup> mutation of Codon17 (A > T) and a full duplication of the α-globin gene cluster, inherited from his mother and father, respectively. Besides, a novel point mutation within the 5' untranslated region of β-Globin (<i>HBB</i>: c. -175 (G > A) was only detected in the patient. This study suggests that lpWGS seems a powerful alternative to detect large CNVs related to thalassemia with second intention for more information of the breakpoints and a simultaneous genome-scale detection of other pathogenic CNVs.</p>","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":null,"pages":null},"PeriodicalIF":1.2000,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hemoglobin","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/03630269.2024.2346143","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Copy number variations (CNVs) involving the α-globin gene cluster can lead to an imbalance in the proportion of α- and β-globin chains and consequently cause clinical symptoms of β-thalassemia. In our case, a 6-year-old boy, clinically diagnosed with β thalassemia intermedia, was admitted for further genetic diagnosis with his family. Targeted sequencing and third generation sequencing (TGS) were used to detect the possible variants of the thalassemia genes. Low-pass whole genome sequencing (lpWGS) was conducted to specify the exact location of relevant CNVs across the genome, which was then validated by multiplex ligation-dependent probe amplification.The results revealed that the patient had a heterozygous β0 mutation of Codon17 (A > T) and a full duplication of the α-globin gene cluster, inherited from his mother and father, respectively. Besides, a novel point mutation within the 5' untranslated region of β-Globin (HBB: c. -175 (G > A) was only detected in the patient. This study suggests that lpWGS seems a powerful alternative to detect large CNVs related to thalassemia with second intention for more information of the breakpoints and a simultaneous genome-scale detection of other pathogenic CNVs.
期刊介绍:
Hemoglobin is a journal in the English language for the communication of research and information concerning hemoglobin in humans and other species. Hemoglobin publishes articles, reviews, points of view
The journal covers topics such as:
structure, function, genetics and evolution of hemoglobins
biochemical and biophysical properties of hemoglobin molecules
characterization of hemoglobin disorders (variants and thalassemias),
consequences and treatment of hemoglobin disorders
epidemiology and prevention of hemoglobin disorders (neo-natal and adult screening)
modulating factors
methodology used for diagnosis of hemoglobin disorders