OBJECTIVE: To investigate the genotype distribution of thalassemia in the population of childbearing age in Yulin area. METHODS: The polymerase reaction (PCR) combined with agargel eletrophoresis and reserve dot bolt hybridization was used to detected the α- and β-thalassemia gene in 31 769 cases of suspected thalassemia population at childbearing-age. RESULTS: A total of 22 254 cases were identified as thalassemia gene detetion or mutation in 31 769 cases with a detecting rate of 70.05%, and the detecting rate of α-thalassemia, β-thalassemia and α-combining β-thalassemia were 45.86% (14 569/31 769), 19.45% (6 178/31 769) and 4.74% (1 507/31 769) respectively. 28 kinds of α-thalassemia gene mutations were detected, the common mutations were as follows: -- CONCLUSION The detection rate of thalassemia gene is high in Yulin caildbearing-age population, and there is diversity in mutation spectrums of thalassemia. The most common genotypes are --
China ; Genotype ; Humans ; Mutation ; alpha-Thalassemia/genetics* ; beta-Thalassemia/genetics*

OBJECTIVE: To explore the cause of inconsistent genotypes for an α-thalassemia carrier by using two commercial genotyping kits. METHODS: GAP-PCR and PCR-reverse dot blotting (PCR-RDB) were employed to determine the genotype of the carrier, while Sanger sequencing was used to verify the results. RESULTS: Sequencing analysis demonstrated that the subject has carried a α1 globin gene with a 3.7 kb heterozygous deletion. In addition, two novel mutations, IVS-II-55(T>G) and IVS-II-119(G>TCGGCCC), were found in intron 2 of α2 globin gene. CONCLUSION The two mutations located in the binding regions of PCR primers have caused failure of PCR amplification and misreading of the genotype. Combination of clinical and hematological phenotypes is indispensible to infer the genotype of carriers for accurate diagnosis.
Genotype ; Heterozygote ; Humans ; Mutation ; alpha-Thalassemia ; genetics

OBJECTIVETo detect rare types of thalassemia mutations among southern Chinese population.

METHODSPeripheral blood samples from 327 patients from various regions of southern China were collected. The patients were suspected as rare-type thalassemia for their inconsistency between hematological phenotypes and results of routine mutation screening. The samples were further analyzed with GAP-PCR and DNA sequencing.

RESULTSOne hundred and eight cases were diagnosed as rare types of thalassemia. Among whom 10 rare α-globin gene mutations including --THAI, HKα, αααanti3.7, αααanti4.2, -α2.8, -α27.6, CD74 GAC>CAC (Hb Q-Thailand), CD30 (-GAG), CD31 AGG>AAG and CD118 (+TCA), and 12 rare β-globin gene mutations including CD37 TGG>TAG, CD39 CAG>TAG/CD39 CAG>TAG, β II-2 (-T), -90(C>T), -31(A>C), -88(C>T), CD7(-A), CD138(+T), CD89-93 (--AGTGAGCTGCACTG), CD54-58 (-TATGGGCAACCCT), Chinese G γ +(A γδβ)0 and Vietnamese HPFH (HPFH-6) were identified. -88(C>T) (HBB: c.-138C>T) and CD39 CAG>TAG (HBB: c.118C>T) were discovered for the first time in Chinese population. CD7(-A) (HBB: c.23delA) and CD138(+T) (HBB: c.416_417insT) were new types of β-globin gene mutations.

CONCLUSIONThe present study have enriched the mutation spectrum of thalassemia in southern China, which has provided necessary information for its diagnosis.

Humans ; Mutation ; Thalassemia ; genetics ; alpha-Globins ; genetics ; beta-Globins ; genetics

OBJECTIVE: To assess the value of high-throughput sequencing for the detection of thalassemia-associated variants in ethnic Li minority areas of Hainan, China. METHODS: In Baoting Li and Miao Autonomous County of Hainan Province, 1842 middle school students were randomly selected as the subjects, which included 1249 ethnic Lis, 454 ethnic Hans, and 139 individuals from other ethnic minorities. With DNA extracted from peripheral blood samples, gap-PCR combined with high-throughput sequencing were carried out to detect potential variants of the globin genes. RESULTS: In total 22 α-thalassemia genotypes, 5β-thalassemia genotypes, and 21 α-composite β-thalassemia genotypes were detected. The carrier rates for ethnic Li, ethnic Han and other ethnic minorities were 78.14%, 24.01%, and 28.06%, respectively. In addition, 22 fusion genes, 8 variants leading to abnormal hemoglobin, and 10 rare mutations were identified. CONCLUSION High-throughput sequencing can detect a wide range of genetic variants associated with thalassemia in the ethnic Li minority areas and has played an important role for the identification of fusion genes, variants underlying hemoglobin anomalies and rare mutations.
Humans ; alpha-Thalassemia/genetics* ; Genotype ; Ethnicity/genetics* ; Mutation ; High-Throughput Nucleotide Sequencing ; China ; beta-Thalassemia/genetics*

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.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

OBJECTIVE: To investigate the gene mutation and genotype distribution of thalassemia in the population of childbearing age in Chongzuo area of Guangxi. METHODS: Six α-thalassemia and 17 β-thalassemia gene mutations common in Chinese were detected by gap-polymerase chain reaction (gap-PCR) combined with agarose gel eletrophoresis and reserve dot bolt hybridization in 29 266 cases of child-bearing age suspected of thalassemia. RESULTS: A total of 19 128 (65.36%) cases were identified with thalassemia. The detection rate of α-thalassemia, β-thalassemia and α-combining β-thalassemia was 45.25% (13 242/29 266), 15.47% (4 526/29 266) and 4.65% (1 360/29 266), respectively. A total carrying rate of 8 kinds of α-thalassemia gene mutations was 26.74% (15 649/58 532), including 12.51% for --^SEA, followed by 5.70% for -α^3.7, and 0.24% for --^Thai. Among 32 α-thalassemia genotypes, the most common five were --^SEA/αα, -α^3.7/αα, α^CSα/αα, -α^4.2/αα and α^WSα/αα, accounting for 47.27%, 18.31%, 8.56%, 8.52% and 7.91%, respectively, as well as 0.97% for --^Thai/αα. A total carrying rate of 13 kinds of β-thalassemia gene mutations was 10.07% (5 897/58 532), including 3.63% for CD41-42, followed by 2.55% for CD17, and 0.003% for -50 (G>A). Among 17 β-thalassemia genotypes, the most common six were CD41-42/N, CD17/N, CD71-72/N, CD26/N, 28/N and IVSI-1/N, accounting for 36.15%, 25.81%, 9.43%, 8.18%, 8.09% and 7.75%. The homozygous genotype CD26/CD26 [hemoglobin (Hb): 121 g/L] and -28/-28 (Hb: 56 g/L) were respectively detected in one case, and double heterozygous genotype were detected in 5 cases, including 3 cases of CD41-42/CD26 (Hb: 41 g/L, 51 g/L, 63 g/L, respectively), 1 case of -28/IVSI-1 (Hb: 53 g/L), and 1 case of CD71-72/CD26 (Hb: 89 g/L), in which patients with moderate or severe anemia had a history of blood transfusion. Among 104 α-combining β-thalassemia genotypes, the most common were --^SEA/αα, -α^3.7/αα combining CD41-42/N and --^SEA/αα combining CD17/N, accounting for 12.13%, 9.63% and 9.26%, respectively. In addition, 1 case of --^SEA/-α^3.7 combining -28/IVSI-1 (Hb: 83 g/L) and 1 case of -α^3.7/αα combining CD41-42/ CD41-42 (Hb: 110 g/L) were detected without history of blood transfusion, while 1 case of α^WSα/αα combining CD41-42/CD17 (Hb: 79 g/L) and 1 case of --^SEA/αα combining CD17/-28 (Hb: 46 g/L) were detected with history. CONCLUSIONS The detection rate of thalassemia genes is high and the mutations are diverse in the population of childbearing age in Chongzuo area of Guangxi. The common deletion genotype is --^SEA/αα in α-thalassemia and CD41-42/N in β-thalassemia, and deletion genotype --^Thai is not rare. There is a certain incidence of intermediate and severe β-thalassemia, and most patients require transfusion therapy. The results are beneficial for genetic consultation and intervention of thalassemia.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Dipeptidyl Peptidase 4/genetics* ; China/epidemiology* ; Genotype ; Mutation

OBJECTIVETo describe a community-based model for prevention and control of severe alpha and beta thalassemias in Zhuhai city of Guangdong province.

METHODSCouples for premarital medical examination or regular healthcare examination in pregnancy were enrolled in this prospective screening program, which was supported by the two-level network composed of 6 local hospitals for testing thalassemias and follow-up for genetic counseling. A conventional heterozygote screening strategy was used to determine alpha and beta thalassemia traits in women and their partners according to the standard procedures of hematological phenotype analysis. Then confirmative diagnosis of alpha and beta thalassemia was performed on those couples suspected at-risk for severe thalassemia by using the PCR-based molecular diagnostic assays. The couples at-risk for severe thalassemia were counseled and offered prenatal diagnosis and termination of pregnancy in case of an affected fetus.

RESULTSDuring the period between January 1998 and December 2005, the screened records included 85522 young females and their partners for premarital screening and 10439 pregnant women for prenatal screening, with 71.38% coverage of total population recorded in this city for premarital screening. Six thousands five hundreds and sixty-three individuals in total were found to be the carriers of thalassemias, with 4312 for alpha thalassemia (4.5%) and 2251 for beta thalassemia (2.3%), respectively. One hundred and forty-eight couples were diagnosed to be at-risk for thalassemias, including 103 for alpha thalassemia and 45 for beta thalassemia, respectively. Successful prenatal diagnosis was made for 142 (98 for alpha thalassemia and 44 for beta thalassemia) out of 148 (95.9%) pregnancies at-risk for severe thalassemias. Twenty-three cases of hydrops fetalis, 4 of Hb H diseases and 14 of beta thalassemia were identified. All 41 pregnancies with affected fetuses were voluntarily terminated. Thus, this has led to a marked decrease of severe thalassemia syndrome since the program started.

CONCLUSIONWe presented the first community-based prospective screening program in China for control of alpha and beta thalassemia in Zhuhai city with a population of 1.29 million through premarital or prenatal screening. This model could be used for control of thalassemias and other hemoglobinopathies in other regions of China and also in other developing countries.

China ; Humans ; Prenatal Diagnosis ; methods ; alpha-Thalassemia ; diagnosis ; genetics ; beta-Thalassemia ; diagnosis ; genetics

OBJECTIVE: To investigate the types and proportion of gene mutations of thalassemia in Hakka people in Gannan Area of Jiangxi, and to provide some references for prevention and treatment of thalassemia major, genetic counseling and epidemiological studies. METHODS: 81 cases Hakka patients with severe thalassemia admitted treated in First Affiliated Hospital of Gannan Medical College from January 2009 to June 2019 were enrolled. The deletion type of α-thalassemia was detected by Gap-PCR. The point mutations of α-thalassemia and β-thalassemia were detected by PCR-RDB. The thalassemia gene was detected and analyzed in the patients with anemia, and the frequency of gene mutation was calculated. RESULTS: Among 81 Hakka patients with thalassemia major, 4 β-thalassemia (homozygote) genotypes were detected out, including: CD41-42（TTCT）(19 cases), β-IVS-II-654 (C→T) (9 cases), -28M (A→G) (1 case), CD17 (A→T) (1 case); 12 β-thalassemithalassemia (heterozygote) genotypes were detected out, including: CD41-42(-TTCT)/β-IVS-II-654(C→T) (15 cases, 29.41%), β-IVS-II-654(C→T)/β-28M(A→G) (13 cases，25.49%) ； CD41-42(-TTCT)/β-28M(A→G) (9 cases，17.65%); β-IVS-II-654(C→T) /CD27/28(+C) (3 cases， 5.88%) ； CD41-42(-TTCT)/CD27/28(+C)(3 case，5.88%)；β-28M(A→G)/CD17(A→T) (2 cases，3.92%)；CD41-42(-TTCT)/CD17(A→T), CD41-42(-TTCT)/Βe, β-IVS-II-654(C→T)/β-29、βCD17（A→T）/CD71-72(+a), βCD71-72/β-28M(A→G), β-28M(A→G) /β-IVS-II-654(C→T)(1 cases，1.96%). There were 3 cases of β homozygous thalassemia with α-thalassemia gene and 5 cases of β heterozygotes thalassemia with α-thalassemia gene. CONCLUSION The incidence rate of thalassemia in Hakka people in Gannan Area of Jiangxi is relatively high. The distribution of gene mutation types is as follows: the genotype of CD41-42 (-TTCT) is the main genotype of β-thalassemia (homozygous); the major genotypes of β- thalassemia (heterozygotes) are CD41-42 (-TTCT)/β-IVS-II-654 (C→T) and β-IVS-II-654 (C→T) /β-28M (A→G); CD41-42 (-TTCT) gene is dominant in β-complex α-thalassemia.
China ; Genotype ; Heterozygote ; Humans ; Mutation ; alpha-Thalassemia/genetics* ; beta-Thalassemia/genetics*

OBJECTIVE: To analyze the hematological characteristics of Hb Broomhill and Hb Hornchurch, and prenatal diagnosis should be carried out in two families. METHODS: RBC parameters and hemoglobin electrophoretogram were analyzed on the peripheral blood of all patients, and amniotic fluid was collected for prenatal diagnosis. PCR-Flow fluorescent hybridization and Sanger sequencing were performed for gene diagnosis of thalassemia. RESULTS: Three cases of Hb Broomhill were detected, including 2 cases with common SEA α-thalassemia, which was characterized by hypochromic microcytic mild anemia, the capillary electrophoregram revealed a tiny shoulder peak before the Hb A peak; 1 case was diagnosed as Hb Hornchurch combined with β-thalassemia, which also showed mild anemia. Hemoglobin electrophoretogram showed an abnormal hemoglobin variant peak at Hb A CONCLUSION The carriers of Hb Broomhill and Hb Hornchurch do not have microcytic hypochromic anemia, which do not aggravate the hematological symptoms, such as anemia when being combined with thalassemia of the same type.
Anemia, Hypochromic ; Hemoglobins, Abnormal/genetics* ; Heterozygote ; Humans ; alpha-Thalassemia/genetics* ; beta-Thalassemia

OBJECTIVE: To analyze the gene defect types and distribution characteristics of α- and β-thalassemia in Lingui District of Guilin City, Guangxi, so as to provide scientific basis for genetic consultation and prevention measures. METHODS: A total of 6 496 suspected cases for screening the thalassemia during physical examination, premarital examination, pregnancy examination and hospitalization in the Second Affiliated Hospital of Guilin Medical University from May 2016 to October 2019 were analyzed. Gap-PCR, PCR-RDB and DNA sequencing techniques were used to detect the types and constituent ratios of gene defects in α- and β-thalassemia positive cases. RESULTS: Among 6 496 suspected patients, 1 363 were thalassemia carriers, the total positive rate was 20.98%. There were 677 cases of single-gene deletion and 26 cases of double-gene detetion on the deletional α-thalassemia, 115 cases of non-deletion α-thalassemia mutation and 4 cases of deletion plus mutation. The positive rate of α-thalassemia was 12.66%. There were 11 gene abnormalities for α-thalassemia, of which -- CONCLUSION Lingui district of Guilin city is a high incidence area of thalassemia. The mutation rate of α-thalassemia --
China/epidemiology* ; Female ; Genotype ; Heterozygote ; Humans ; Mutation ; Pregnancy ; alpha-Thalassemia/genetics* ; beta-Thalassemia/genetics*