Thalassemia, a human blood disorder / Talassemia, uma doença do sangue humano

Abstract A group of inherited blood defects is known as Thalassemia is among the world's most prevalent hemoglobinopathies. Thalassemias are of two types such as Alpha and Beta Thalassemia. The cause of these defects is gene mutations leading to low levels and/or malfunctioning α and β globin proteins, respectively. In some cases, one of these proteins may be completely absent. α and β globin chains form a globin fold or pocket for heme (Fe++) attachment to carry oxygen. Genes for alpha and beta-globin proteins are present in the form of a cluster on chromosome 16 and 11, respectively. Different globin genes are used at different stages in the life course. During embryonic and fetal developmental stages, γ globin proteins partner with α globin and are later replaced by β globin protein. Globin chain imbalances result in hemolysis and impede erythropoiesis. Individuals showing mild symptoms include carriers of alpha thalassemia or the people bearing alpha or beta-thalassemia trait. Alpha thalassemia causes conditions like hemolytic anemia or fatal hydrops fetalis depending upon the severity of the disease. Beta thalassemia major results in hemolytic anemia, growth retardation, and skeletal aberrations in early childhood. Children affected by this disorder need regular blood transfusions throughout their lives. Patients that depend on blood transfusion usually develop iron overload that causes other complications in the body systems like renal or hepatic impairment therefore, thalassemias are now categorized as a syndrome. The only cure for Thalassemias would be a bone marrow transplant, or gene therapy with currently no significant success rate. A thorough understanding of the molecular basis of this syndrome may provide novel insights and ideas for its treatment, as scientists have still been unable to find a permanent cure for this deadly disease after more than 87 years since it is first described in 1925.

Resumo Um grupo de defeitos sanguíneos hereditários é conhecido como talassemia e está entre as hemoglobinopatias mais prevalentes do mundo. As talassemias são de dois tipos, como talassemia alfa e beta. As causas desses defeitos são as mutações genéticas que levam a níveis baixos e/ou proteínas de globina com mau funcionamento, respectivamente. Em alguns casos, uma dessas proteínas pode estar completamente ausente. As cadeias de globina α e β formam uma dobra ou bolsa de globina para a fixação de heme (Fe ++) para transportar oxigênio. Os genes das proteínas alfa e beta globina estão presentes na forma de um cluster nos cromossomos 16 e 11, respectivamente. Diferentes genes de globina são usados ​​em diferentes estágios do curso de vida. Durante os estágios de desenvolvimento embrionário e fetal, as proteínas γ globina se associam à α globina e, posteriormente, são substituídas pela proteína β globina. Os desequilíbrios da cadeia de globina resultam em hemólise e impedem a eritropoiese. Indivíduos que apresentam sintomas leves incluem portadores de talassemia alfa ou as pessoas com traços de talassemia alfa ou beta. A talassemia alfa causa condições como anemia hemolítica ou hidropsia fetal fatal, dependendo da gravidade da doença. A beta talassemia principal resulta em anemia hemolítica, retardo de crescimento e aberrações esqueléticas na primeira infância. As crianças afetadas por esse distúrbio precisam de transfusões de sangue regulares ao longo da vida. Os pacientes que dependem de transfusão de sangue geralmente desenvolvem sobrecarga de ferro que causa outras complicações nos sistemas do corpo, como insuficiência renal ou hepática, portanto as talassemias agora são classificadas como uma síndrome. A única cura para as talassemias seria um transplante de medula óssea ou terapia genética sem atualmente uma taxa de sucesso significativa. Uma compreensão completa da base molecular dessa síndrome pode fornecer novos insights e ideias para seu tratamento, já que os cientistas ainda não conseguiram encontrar uma cura permanente para essa doença mortal depois de mais de 87 anos desde que foi descrita pela primeira vez em 1925.

Causes of Abnormal Hemoglobin Electrophoresis / 中国实验血液学杂志

OBJECTIVE@#To investigate the possible causes of abnormal hemoglobin electrophoresis results.@*METHODS@#The hemoglobin electrophoresis results of 5 696 patients in the First Affiliated Hospital of Chengdu Medical College from September 2018 to July 2021 were collected, and the abnormal results and clinical significance were analyzed.@*RESULTS@#The results of 486 patients (accounting for 8.53%) were abnormal, of which 300 cases had increased HbA2, 135 cases had decreased HbA2, 44 cases had increased F alone, and 7 cases had abnormal hemoglobin bands. Among the 486 patients, 246 patients were thalassemia gene positive (the positive rate was 50.62%), including 29 cases of α thalassemia, 208 cases of β thalassemia and 9 cases of αβ thalassemia. Among the patients with elevated HbA2, 68.67% were detected β thalassemia, 3.00% αβ thalassemia, 9.33% were suspected to be caused by macrocytosis, 6.33% by thyroid dysfunction, and 12.67% by uncertainty of the method. Among the patients with reduced HbA2, 21.48% were detected α thalassemia, 60.00% iron deficiency anemia, 8.15% were suspected to be caused by thyroid dysfunction, and 10.37% by uncertainty of the method. Among the patients with elevated F alone, the results of thalassemia gene detection were negative, 40.91% of them were suspected to be caused by macrocytosis, 27.27% by hereditary persistence of fetal hemoglobin, 29.55% by special physiological condition of pregnant women, and 2.27% by hyperthyroidism. Abnormal hemoglobin bands were detected in 7 patients, including 4 cases of hemoglobin D, 2 cases of hemoglobin E, and 1 case of hemoglobin J.@*CONCLUSION@#Thalassemia, iron deficiency anemia, macrocytosis such as megaloblastic anemia and non-severe aplastic anemia, thyroid dysfunction, hereditary persistence of fetal hemoglobin, abnormal hemoglobin diseases, the uncertainty of the method are all important causes of abnormal hemoglobin electrophoresis results. In clinical work, the patient's indicators should be comprehensively analyzed to determine the possible cause.

Genotype and Phenotype of α-Thalassemia Fusion Gene in Huadu District of Guangzhou, Guangdong Province of China / 中国实验血液学杂志

OBJECTIVE@#To explore the carrier rate, genotype and phenotype of α-thalassemia fusion gene in Huadu district of Guangzhou, Guangdong province of China, and provide data reference for the prevention and control of thalassemia.@*METHODS@#A total of 10 769 samples who were screened for thalassemia in Maternal and Child Health Hospital of Huadu District from July 2019 to November 2020 were analyzed retrospectively. Blood cell analysis and hemoglobin (Hb) electrophoresis were performed. Thalassemia genes were analyzed by gap-PCR and PCR-reverse dot blot hybridization (PCR-RDB).@*RESULTS@#A total of 9 cases with α-thalassemia fusion gene were detected in 10 769 samples (0.08%). There were 7 cases with fusion gene heterozygote, 1 case with compound of α-thalassemia fusion gene and Hb G-Honolulu, 1 case with compound of α-thalassemia fusion gene and Hb QS. The MCV results of 4 samples of blood cell analysis were within the reference range, the Hb A2 value of 1 case was decreased, and there were no other abnormalities found.@*CONCLUSION@#The α-thalassemia fusion gene is common in Huadu district of Guangzhou, and heterozygotes are more common, and current screening methods easily lead to misdiagnosis.

Epidemiological Survey of Hemoglobinopathies Based on Next-Generation Sequencing Platform in Hunan Province, China / 生物医学与环境科学（英文）

OBJECTIVE@#This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province.@*METHODS@#We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed.@*RESULTS@#The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α 3.7/αα (50.23%) and β IVS-II-654/β N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively.@*CONCLUSION@#Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.

Association of FOXO3 polymorphism (rs3800231) and clinical subphenotypes of beta thalassemic individuals

Abstract Introduction Studies have shown that the loss of the FOXO3 transcriptional function is involved in the pathophysiology of some chronic erythroid disorders, including beta-thalassemia (β-thal). Therefore, the single nucleotide polymorphism (SNP) rs3800231 (35-2764A > G) could contribute to alterations in its transcriptional activity, acting as a modifier of β-thal phenotypic manifestations. Objective and method In order to better understand the genotypic and/or allelic distributions among β-thal patients, we evaluated 83 β-thal heterozygous and 20 homozygous, compared to 117 individuals without hemoglobinopathies (control group). Additionally, we verified any influence of the FOXO3 polymorphism on clinical manifestations among β-thal homozygotes. Results We obtained higher frequencies of the wild-type homozygous (AA) and the wild-type allele (A) in the β-thal group (p< 0.0001 and p= 0.00014, respectively). The most common clinical manifestations found among β-thal homozygotes were iron overload (90%), splenomegaly (65%) and bone complications (35%), e.g., osteopenia/osteoporosis. We observed that close to 80% of the patients presenting such manifestations had the genotype AA. However, we did not find any significant involvement of the FOXO3 polymorphism in clinical manifestation occurrences. Conclusion Thus, we concluded that the SNP rs3800231 did not play a significant role as a modifier of the clinical manifestations observed in the β-thal homozygotes studied.

Thalassemia Gene Detection Results and Application Value of Hematological Indexes Among Pregnant Women in Xindu District of Chengdu City / 中国实验血液学杂志

OBJECTIVE@#To analyze the genotype characteristics of α- and β-thalassemia and the diagnostic value of hematological indexes in pregnant women in Xindu District of Chengdu.@*METHODS@#The blood routine parameters(MCV) <80 fl and (or) (MCH) <27 pg and hemoglobin electrophoresis were used to screen the pregnant women, PCR-reverse dot blot hybridization(PCR-RDB) technique was used to detect the common α- and β-thalassemia gene types in the primary screening positive population. The husbands of the diagnosed pregnant women were recalled for gene testing, and the highly suspected patients were checked by gene sequencing.@*RESULTS@#Among the 7 049 pregnant women, 1 740(24.68%) cases were positive for primary screening. 180 patients were diagnosed as thalassemia gene positive, among them, 94 cases (52.22%) of α-thalassemia were detected and six genotypes were found, in which --SEA /αα genotype was the highest (58 cases, 61.70%); 82 cases (45.56%) of β-thalassemia were detected and ten genotypes were found while CD41-42/N and CD17/N genotypes were the most common; there were 4 cases(2.22%) with α combined with β-thalassemia. Through clinical follow-up survey, there were 4 couples with the same type of thalassemia, one of them was induced labor after diagnosis of hemoglobin H disease. Receiver operating curve (ROC curve) was used to analyze the diagnostic value of hematological parameters in thalassemia positive pregnant women. The results showed that AUC(HBA2)<AUC(MCHC)<AUC(RDW-SD)<AUC(MCH)<AUC(MCV) (P<0.01).@*CONCLUSION@#The most common genotypes of α- and β-thalassemia in pregnant women in Xindu District of Chengdu were --SEA /αα, CD41-42/N, CD17/N. The blood routine indicators (HBA2、RDW-SD、MCHC、MCH、MCV) have high diagnostic value for screening of thalassemia.

Clinical Diagnosis and Prenatal Screening of Hb Lepore-BW Associated with IVS-II-654 Heterozygous Mutation / 中国实验血液学杂志

OBJECTIVE@#To identify one case of rare Hb Lepore-BW associated with IVS-II-654 heterozygous mutation in Sichuan area.@*METHODS@#The blood routine examination and hemoglobin electrophoresis methods were used to analyze the blood routine parameters, HbA2 and HbF in the samples of peripheral blood in proband and his parents, as well as the cord blood of pregnant woman. The detection of thalassemia gene and Sanger sequencing methods were used to detect the hemoglobin mutations.@*RESULTS@#The result showed that the Hb Lepore-BW heterozygous mutation was detected in the father of the proband, while a rare Hb Lepore-BW with IVS-II-654 heterozygous mutation was detected in the proband, as well as his mother and cord blood were both detected as IVS-II-654 heterozygous mutation.@*CONCLUSION@#The study identified a rare Hb Lepore-BW with IVS-II-654 heterozygous mutation, which was characterized by intermediate β-thalassemia. It is necessary to hemoglobin electrophoresis combined with routine blood testing in prenatal screening.

Genetic Analysis and Prenatal Diagnosis of Thalassemia in Couples of Childbearing Age in Quanzhou Region Fujian Province, China / 中国实验血液学杂志

OBJECTIVE@#To explore the genotypes and prenatal diagnosis of thalassemia in couples of childbearing age in Quanzhou, Fujian Province.@*METHODS@#Blood routine and hemoglobin electrophoresis were performed for initial thalassemia screening in 76 328 couples in Quanzhou region from July 2017 to July 2020. The couples with positive initial screening results further underwent thalassemia gene test. Couples carrying homotypic thalassemia genes underwent prenatal diagnosis in the second trimester.@*RESULTS@#Among 76 328 couples of childbearing age, 1 809 couples of positive initial thalassemia screening were identified, with the positive rate about 2.37%. Further results of genetic detection of the 1 809 couples showed that 985 cases were diagnosed as α- thalassemia, of which --sea/αα was the most frequency, followed by -α3.7/αα and ααQS/αα; 296 cases were diagnosed as β-thalassemia, the most frequency mutations were 654M/N and 41-42M/N; 26 cases of compound α and β-thalassemia were detected. In addition, 3 rare cases of thalassemia were detected, including --THAI/αα, SEA-HPFH, and -α6.9/--sea. Among them, 108 couples were confirmed as homologous thalassemia, with the detection rate about 5.97%, including 96 couples of homologous α-thalassemia, 9 couples of homologous β-thalassemia, and 3 couples with one had compound α- and β-thalassemia. Among them, 17 couples with homologous α-thalassemia underwent prenatal diagnosis in the second trimester, of which 1 case of Hb Bart's Hydrops Syndrome, 3 cases of HbH disease, 9 cases of silent thalassemia or α-thalassemia minor, and 4 cases of healthy fetuses were detected. Fetal chromosome karyotype analysis showed that 16 cases were normal and 1 case diagnosed as Down syndrome.@*CONCLUSION@#Thalassemia screening in pre-marital and pre-pregnancy, and prenatal diagnosis can effectively reduce the birth of children with thalassemia intermediate and thalassemia major. It is necessary to perform chromosome karyotype analysis at the same time as prenatal diagnosis of thalassemia gene in order to avoid fetus with abnormal chromosome.

Genetic Analysis of Thalassemia in 22 940 Pregnant Women in Xiangxi Tujia and Miao Autonomous Prefecture / 中国实验血液学杂志

OBJECTIVE@#To investigate the incidence and types of thalassemia in Xiangxi Tujia and Miao Autonomous Prefecture.@*METHODS@#Automatic capillary electrophoresis was used to screen the thalassemia phenotypes of 22 940 blood samples of pregnant women and puerperants collected in our hospital and some other medical institutions in the prefecture during 2017-2019, among which there were 3 356 cases of Tujia ethnicity, 2 821 cases of Miao ethnicity, and 2 233 cases of Han ethnicity included, whose ethnicity were indicated. The samples with positive result would undergo further genetic testing.@*RESULTS@#There were 2 314 cases of suspicious thalassemia were screened from 22 940 cases by the electrophoresis, thus the positive rate was 10.1% (hematological phenotypes from some other institutions were not included). Specifically, there were 1 706 cases with HBA2 less than 2.5%, 255 cases with HBA2 ranged from 2.5% to 3.5%, which displayed abnormal hematology (MCV or/and MCH) or other abnormal bands, and 353 cases with HBA2>3.5%. There were 436 suspected positive patients in 2 314 suspicious samples received further thalassemia gene testing in our hospital, among them 48 cases were diagnosed with α-thalassemia, 85 cases with β-thalassemia, and 2 cases as compound type. The positive diagnosis rate of α-thalassemia gene test was 11.0%, β-thalassemia was 19.4%, and positive pregnant women was 31.0%.@*CONCLUSION@#The positive rate of thalassemia screening in Xiangxi Autonomous Prefecture is roughly the same as that in other regions of Hunan. The positive predictive value of β-thalassemia screening is as high as 86%. Compared with the missed screening data, it is recommended to use hematology (MCV, MCH) method combined with capillary hemoglobin electrophoresis for thalassemia screening.

The value of combined detection of HbA2 and HbF for the screening of thalassemia among individuals of childbearing ages / 中华医学遗传学杂志

OBJECTIVE@#To assess the application value of combined detection of HbA2 and HbF for the screening of thalassemia among a population of childbearing age in Quanzhou, Fujian, and determine the optimal cut-off values for the region.@*METHODS@#Capillary hemoglobin electrophoresis and genetic testing for α and β globin gene mutations were simultaneously carried out on 11 428 patients with suspected thalassemia. Statistical methods were used to analyze the distribution of various types of thalassemia and compare the performance of HbA2 and HbF measurement for the screening of various types of thalassemia. The optimal cut-off values for HbA2 and HbF were determined with the ROC curves.@*RESULTS@#4591 patients with α, β, and αβ compound thalassemia were identified by genetic testing. The most common genotypes for α and β thalassemia included --SEA/αα and β654/βN, β41-42/βN, and β17/βN. The ROC curves were drawn to compare the performance of HbA2 screening for α-, β-, αβ-compound, static α-, mild α-, and intermediate α-thalassemia, and the maximum area under the curves was 0.674, 0.984, 0.936, 0.499, 0.731, 0.956, and the optimal cut-off values for HbA2 were 2.45%, 3.25%, 3.65%, 2.95%, 2.55%, 1.75%, respectively.@*CONCLUSION@#HbA2 is an efficient indicator for identifying intermediate types of α-, β-, and αβ compound thalassemia. The combination of HbA2 and HbF measurement can effectively detect carriers for β-thalassemia mutations.

Preimplantation Genetic Diagnosis of α/β Complex Thalassemia by Next Generation Sequencing / 中国实验血液学杂志

OBJECTIVE@#To explore the application value of next generation sequencing (NGS) in preimplantation genetic diagnosis of α/β complex thalassemia couple.@*METHODS@#The coding regions of α-globin genes (HBA1, HBA2) and β-globin gene (HBB) were selected as the target regions. The high-density and closely linked single nucleotide polymorphism (SNP) sites were selected as the genetic linkage markers in the upstream and downstream 2M regions of the gene. After NGS, the effective SNP sites were selected to construct the haplotype of the couple, and the risk chromosome of the mutation carried by the couple was determined. The NGS technology was used to sequence the variations of HBA1, HBA2 and HBB directly and construct haplotype linkage analysis for preimplantation genetic diagnosis.@*RESULTS@#Direct sequencing and haplotype linkage analysis of HBA1, HBA2 and HBB showed that two of the six blastocysts were α/β complex thalassemia, one was β-thalassemia heterozygote, two were α-thalassemias heterozygotes, and one was intermediate α-thalassemia. A well-developed embryo underwent preimplantation genetic diagnosis was implanted into the mother's uterus, and a healthy infant was born at term.@*CONCLUSION@#Preimplantation genetic diagnosis can be carried out by NGS technology in α/β complex thalassemia couples, and abortion caused by aneuploid embryo selection can be avoided.

Genetic Effect Analysis of β-globin Gene 3'UTR+101G>C (HBB:c. *233G>C) Variant / 中国实验血液学杂志

OBJECTIVE@#To investigate whether β-globin gene 3'UTR+101G>C (HBB:c.*233G>C) variant has genetic effect and provide basis for gene diagnosis and genetic counseling.@*METHOD@#Whole blood cell analysis and capillary zone electrophoresis (CZE) were used to analyze the hematological indexes. The most frequent 23 mutations in southern Chinese individuals were routinely measured by PCR-flow fluorenscence immunmicrobeads assay. Sanger sequencing was used to detect the other variants of β-globin gene (HBB).@*RESULTS@#In 463 cases, a total of 7 cases with HBB:c.*233G>C variant were detected, among them 4 cases carried other pathogenic variants of HBB gene (2 cases were in trans, 2 cases were in cis), who had typical hematological characteristics of mild β-thalassemia, and 3 cases also carried abnormal hemoglobin variation, but did not have hematological characteristics of β-thalassemia.@*CONCLUSION@#The study shows that HBB:c.*233G > C variant has no obvious genetic effect and should be a benign polymorphism.

Genetic Testing for Alpha and Beta Thalassemia in Children in Quanzhou Region of Fujian Province in China / 中国实验血液学杂志

OBJECTIVE@#To analyze the genotypes and distribution of thalassemia in children in Quanzhou Region so as to provide reference for the prevention and control of thalassemia.@*METHODS@#A total of 1 302 children with suspected thalassemia were collected from January 2014 to April 2020 in Quanzhou Region. The deletional α-thalassemia was detected by Gap-PCR, and DNA reverse dot blot (RDB) hybridization was used to detect α- and β-thalassemia mutations.@*RESULTS@#In the 1 302 cases, 667 cases were identified as thalassemia carriers, and the positive detection rate was about 51.23%. Among them, 380 cases of α-thalassemia gene were detected, and --@*CONCLUSION@#There are various genotypes of thalassemia in children in Quanzhou Region, and many children with thalassemia major or intermedia. Therefore, further prevention and control of thalassemia need to be strengthened for reducing the birth of thalassemia major or intermedia.

Differential Diagnosis of Three Commonest Deletion β-Thalassemia in Chinese / 中国实验血液学杂志

OBJECTIVE@#To analyze the hematological characteristics of Chinese @*METHODS@#Hemoglobin electrophoresis and blood routine test were used to analyze the hematological indexes of all peripheral blood samples，PCR-Flow fluorescent hybridization and Gap-PCR were used to detect the globin gene mutations and the data were analyzed statistically.@*RESULTS@#The 3 types of deletion β- Thalassemia patients were showed as hypochromic small cell anemia. The MCH and MCV values of Taiwan type β-thalassemia patients were the lowest. The results of hemoglobin electrophoresis showed that the increasing of HbF was found in all of the 3 types. Except for the decreasing of Hb A2 in Chinese @*CONCLUSION@#Through analyze the hematological characteristics, it can be provide that the guidance for the differential diagnosis and genetic consultation of the three commonest deletion β-thalassemia in Chinese.

Genotypes of thalassemia in children: an analysis of 30 417 cases / 中国当代儿科杂志

OBJECTIVES@#To investigate the distribution of genotypes of thalassemia in children in Guangxi, China.@*METHODS@#A total of 30 417 children with positive results of thalassemia screening in the Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region from January 2011 to December 2019 were enrolled. Single-tube multiplex PCR, agarose gel electrophoresis, and reverse dot blot hybridization technique were used for the detection of common α- and β-thalassemia genes. Gap-PCR or gene sequence analysis was performed for 2 703 children suspected of rare thalassemia.@*RESULTS@#Among the 30 417 children with positive results of thalassemia screening, 23 214 (76.32%) were diagnosed with thalassemia, and the detection rates of α-thalassemia, β-thalassemia, and α-thalassemia with β-thalassemia were 47.77%, 23.75%, and 4.80% respectively. A total of 13 types of α-thalassemia alleles (18 480 alleles in total) were detected, mainly --@*CONCLUSIONS@#There are diverse gene mutations and rich genotypes of thalassemia among children in Guangxi, and α-thalassemia is more common, with --

Effectiveness of Using Mean Corpuscular Volume and Mean Corpuscular Hemoglobin for Beta-thalassemia Carrier Screening in the Guangdong Population of China / 生物医学与环境科学（英文）

Beta (β)-thalassemia is one of the most common hemoglobinopathies worldwide, creating major public health problems and social burdens in many regions. Screening for β-thalassemia carriers is crucial for controlling this condition. To investigate the effectiveness of mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) for screening β-thalassemia, retrospective data were analyzed for 6,779 β-thalassemia carriers subjected to genetic testing following thalassemia screening in Guangdong province between January 2018 and December 2019. Prevalent mutations observed included CD41/42 (-TTCT) (38.43%), IVS-II-654 (C > T) (25.71%), -28 (A > G) (15.78%), CD17 (AAG > TAG) (10.03%), and β

Application of DNA Microarray in Genetic Mutation Detection in Patients with Thalassemia / 中国实验血液学杂志

OBJECTIVE@#To perform dried blood spots thalassemia gene detection in patients with positive blood phenotypes by microarray technology, and evaluate its value in clinical detection.@*METHODS@#DNA samples were extracted from dried blood spots of 410 patients. Microarray technology was used to detect 3 deletion and 3 non-deletion types of α-thalassemia and 19 β-thalassemia point mutations which were common gene mutions in China.@*RESULTS@#There were 357 positive cases in all the 410 tested samples with the positive rate 87.07%, among which 299 cases (72.93%) carried deletion or point mutations of α-thalassemia, 29 cases (7.07%) carried point mutations of β-thalassemia and 29 cases (7.07%) carried gene mutations of complex αβ-thalassemia syndrome. The mutations of α-thalassemia were involved with --@*CONCLUSION@#The most common genetic mutations are --

Gene Detection Analysis of Thalassemia in 2 494 Cases of Childbearing Couples in Haikou City / 中国实验血液学杂志

OBJECTIVE@#To observe the genotypes and composition ratio of thalassemia in couples of reproductive age, and provide a reference for the prevention and control of thalassemia in Haikou.@*METHODS@#Gene diagnosis was performed in 2 494 subjects who were screened for thalassemia before marriage or prenatal by cross-breakpoint PCR, PCR-reverse dot hybridization, and PCR-electrophoresis.@*RESULTS@#A total of 1 037 thalassemia gene carriers were detected in 2 494 samples, with a detection rate of 41.57%, of which 75.02% was α-thalassemia, 18.61% was β-thalassemia, and 6.36% was α-β complex thalassemia. There were 778 cases of α-thalassemia, mainly of deletion type, accounting for 76.99% (599/778). Twenty genotypes were detected, the highest three was --@*CONCLUSION@#In Haikou city, the gene carrying rate of thalassemia is very high, and the genotype distribution is different from other cities in Hainan Province, attention should be paid to the impact of population inflow on the frequency spectrum change of local thalassemia gene.

The Genotypes and Clinical Characteristics of Thalassemia on Children in Wuhan Region / 中国实验血液学杂志

OBJECTIVE@#To investigate the genotypes and clinical characteristics of thalassemia on children in Wuhan region.@*METHODS@#A total of 159 patients diagnosed as thalassemia in Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology from December 2017 to December 2019. The patients were retrospectively analyzed for their types of mutations, detection rates and clinical characteristics.@*RESULTS@#Among the 422 samples, 159 samples were finally diagnosed as thalassemia through genetic testing, the total detection rate was 37.68%. The detection rate of α, β and αβ-thalassemia was 17.30%, 20.14% and 0.24% respectively. Among α-thalassemia, αα/-SEA was the most common one, with a composition ratio of 68.49%(50/73), followed by αα/-α3.7 (19.18%), αα/-α4.2 (6.85%) and αα/ QS (1.37%). 9 types of β-thalassemia gene mutations were detected, and the most common three mutations were IVSII-654(C→T), with a composition ratio of 40.00%, CD41-42(-TTCT) (20.00%) and CD17(A→T)(16.47%). Two novel mutations of β-thalassemia, HBB: c.92-2A＞T and HBB:c.-23A＞G were detected. Among all the positive patients, 134 (84.28%) were 0-3 years old, 19 (11.95%) were 4-6 years old, and 6 (3.77%) were 7 years of age or older. There were 147 patients with mild anemia (92.45%), 11 patients with moderate anemia (6.92%), and 1 patients with severe anemia (0.63%). The MCV of 94(59.12%) patients was lower than 65 fL, and that of 51(32.08%) patients was between 65 fL and 80 fL, while 14(8.81%) patients was higher than 80 fL. MCV in β-thalassemia group was lower than that in α-thalassemia group, and the difference showed statistically significant (P<0.05).@*CONCLUSION@#The genotypes of thalassemia in children in Wuhan area are diverse, and most of them are mild thalassemia, and diagnosed under 3 years old. Children with β-thalassemia have smaller red blood cell volumes than those with α-thalassemia.

Molecular Spectrum of α- and β-Thalassemia among Young Individuals of Marriageable Age in Guangdong Province, China / 生物医学与环境科学（英文）

Thalassemia is a group of genetically heterogeneous diseases characterized by hemolytic anemia. To investigate molecular characteristics of α- and β-thalassemia among young individuals of marriageable age in Guangdong Province, 24,788 subjects with suspected thalassemia were genetically tested for α- and β-thalassemia by Gap-PCR and reverse dot blot during 2018-2019. For suspected rare thalassemia cases, DNA sequencing was performed to identify rare and unknown thalassemia gene mutations. A total of 14,346 thalassemia carriers were detected, including 7,556 cases of α-thalassemia with 25 genotypes and 8 α-gene mutations identified, 5,860 cases of β-thalassemia with 18 genotypes and 18 β-gene mutations identified, and 930 cases of compound α/β-thalassemia. Among them, the frequency of --