α‑thalassemia deletion [‑SEA (Southeast Asian)] and a compound heterozygote for the Chinese Gγ+(Aγδβ)0/βCD17‑thalassemia mutation: A case report
- Authors:
- Published online on: April 18, 2023 https://doi.org/10.3892/mmr.2023.12999
- Article Number: 112
Abstract
Introduction
Thalassemia is a hereditary blood disease common in southern China, and the population carrier rate is 3–24%. It is caused by a disorder in the synthesis of globin chains and can be divided into two main subcategories, α-thalassemia and β-thalassemia, and several rare categories (δ-, γ-, δβ- and εγδβ-thalassemia) (1,2). Compound heterozygotes for β-thalassemia usually have a severe transfusion-dependent phenotype (3). Generally, some conditions that decrease the production of α-globin (α-thalassemia) can reduce the clinical severity (4). The present study reports a case of a 15-year-old Chinese girl carrying compound heterozygosity for Chinese Gγ+(Aγδβ)°/βCD17-thalassemia combined with an -SEA (Southeast Asian) deletion causing a thalassemia intermedia phenotype.
δβ-thalassemia is a rare variant that results from a deletion in both the δ and β globin genes. The deletion causes the fetal γ-globin gene to reopen and continue to be expressed into adulthood, resulting in abnormal levels of fetal hemoglobin (HbF) (5). Within the Chinese population, Chinese type, Yunnan type and Guangzhou type δβ thalassemia have been reported; these are all Gγ+(Aγδβ)°-thalassemia, of which Chinese Gγ+(Aγδβ)°-thalassemia is the most common (6–9). The deletion range of Chinese Gγ+(Aγδβ)°-thalassemia is ~78.9 kb (Fig. 1B), which includes part of the Aγ globin gene, all δ- and β-globin genes, and the DNA sequences with regulatory function downstream of β-globin gene (10). This thalassemia genotype was first reported by Mann et al (11) in the 1970s. However, little research has been focused on its clinical features. To date, only a few cases of compound heterozygous mutations of Chinese Gγ+(Aγδβ)°-thalassemia have been reported, and these cases illustrated normal, moderate or major anemia (12–15). Notably, whether the interaction between Gγ+ (Aγδβ)°-thalassemia and other common β-thalassemia mutations leads to moderate or major clinical phenotypes mainly depends on the type of β-thalassemia allele (β+ or β°).
The present study provides a detailed description of clinical and molecular characteristics in a 15-year-old Chinese girl carrying a compound heterozygosity for Chinese Gγ+(Aγδβ)°/βCD17-thalassemia combined with the-SEA deletion, which represents an example of how combined types of thalassemia affect the clinical severity of Chinese Gγ+(Aγδβ)°-thalassemia.
Materials and methods
Ethical statement
The present study was approved by the ethics committee of Shenzhen Second People's Hospital (Shenzhen, China; approval no. 20210707004) and written informed consent were obtained from the family.
Proband and parents
The proband was a 15-year-old girl from Yulin City, Guangxi, China. 2 ml peripheral blood from the proband and her parents (father, 44 years old; mother, 43 years old) were collected using EDTA as anticoagulant.
Analysis of hematological parameters and hemoglobin (Hb) components
Hematological parameters were analyzed using a Sysmex XN-1,000 automated blood cell counter (Sysmex Corporation). Hb components were tested using a V8 hemoglobin electrophoresis instrument with the V8 Nexus Hemoglobin Ultrascreen kit (Helena Laboratories Corporation).
DNA sample preparation
Genomic DNA was isolated from peripheral blood using an automatic nucleic acid extractor (Xiamen Kaishuo Biological Co., Ltd.) according to the manufacturer's instructions.
Gene analysis
The α-thalassemia deletions (−α3.7, -α4.2, -SEA, -THAI) were analyzed using conventional gap-PCR with deletion type α-thalassemia gene test kit (Shenzhen Yilifang Biological Products Co., Ltd.). The non-deletion α-thalassemia mutations (Hb Constant Spring, Hb Quong Sze and Hb Westmead) were analyzed using conventional PCR-reverse dot blot hybridization (RDB) with non-deletion α-thalassemia gene mutation test kit (Shenzhen Yilifang Biological Products Co., Ltd.). The 19 β-thalassemia mutations, including −28(A>G)(HBB: c.-78A>G), −29 (A>G)(HBB: c.-79A>G), −30 (T>C)(HBB: c.-80T>C), −32 (C>A)(HBB: c.-82C>A), −50(A>G)(HBB: c.-100G>A), codons 14/15 (+G)(HBB: c.45_46insG), codon17(A>T)(HBB: c.52A>T), codon26 (or Hb E)(G>A) (HBB:c.79G>A), codons27/28 (+C)(HBB: c.84_85insC), codon31 (−C) (HBB: c.94delC), codons 37 (G>A)(HBB: c.113G>A), codons 41/42 (−TTCT)(HBB:c.126_129delCTTT), codon43 (G>T)(HBB: c.130G>T),codons71/72 (+A)(HBB: c.216_217insA), IVS-I-1 (G>T)(HBB: c.92 + 1G>T), IVS-I-5 (G>C)(HBB: c.92 + 5G>C), IVS-II-654 (C>T) (HBB: c.316-197C>T), CAP +1 (A>C)(HBB: c.-50A>C) and initiation codon (T>G) (HBB: c.2T>G) were analyzed using conventional RDB with β-thalassemia gene mutation test kit (Shenzhen Yilifang Biological Products Co., Ltd.). Chinese Gγ+(Aγδβ)°-thalassemia was analyzed by gap-PCR according to the manufacturer's instructions. The gap-PCR primer sequences are provided in Table I. Multiplex ligation-dependent probe amplification (MLPA) was performed according to the manufacturer's protocol using a SALSA MLPA Probemix P102 HBB kit (cat. no. P102; MRC-Holland) to further confirm the β-globin gene cluster deletion identified by gap-PCR. PCR reaction mixtures contained 0.1-1 µg of genomic DNA, 0.2 mmol/l each dNTP, 0.2 mmol/l each primer, 20 mmol/l Tris-HCl (pH 8.4), 50 mmol/l KCl, 1.5 mmol/l MgCl2 and 2.5 U of Platinum™ Taq polymerase (Thermo Fisher Scientific, Inc.). After initial denaturation at 95°C for 5 min, a total of 35 PCR cycles were performed under the following PCR conditions: 95°C for 45 sec, 60°C for 30 sec and 72°C for 90 sec; and a final extension at 72°C for 5 min. After amplification, 3 µl of product was run on a 1% agarose gel in 0.5X Tris-Borate-EDTA buffer pre-stained with SYBR Safe (1:10,000; Invitrogen; Thermo Fisher Scientific, Inc.) for 30 min at 5–6 V/cm. After electrophoresis, the gel was visualized using an ultraviolet transilluminator.
DNA sequencing
Two sets of primer pairs were designed and used to amplify and sequence the hemoglobin subunit α genes (HBA1 and HBA2): HBA1, forward 5′-CAAGCATAAACCCTGGCGCGC-3′, and reverse 5′-CCTGGCACGTTTGCTGAG-3′; HBA2, forward 5′-CAAGCATAAACCCTGGCGCGC-3′, and reverse 5′-ATTGTTGGCACATTCCGGGA-3′. The PCR mixture comprised: 50 ng of genomic DNA; up to ddH2O, 30 µl; 10X LA buffer, 5.0 µl; 2.5 mmol/l dNTPs, 3.0 µl; 10 pmol/µl forward primer, 1.0 µl; 10 pmol/µl reverse primer, 1.0 µl; 5 mol/l betaine, 5.0 µl; DMSO, 2.5 µl; 2 U/µl Taq polymerase, 0.4 µl. The C1000 Thermal Cycler (Bio-Rad Laboratories, Inc.) was used with the following thermocycling conditions: Initial denaturation step of 95°C for 5 min, denaturation at 95°C for 40 sec, annealing at 66°C for 30 sec and extension at 72°C for 70 sec, for a total of 33 cycles. DNA sequencing was performed using the Sanger sequencing method, with the reference sequence NC_000011.10. The PCR products were sequenced using an ABI PRISM™ 3,130×l Genetic Analyzer (Applied Biosystems; Thermo Fisher Scientific, Inc.). Sequencing results are shown in Fig. S1, Fig. S2, Fig. S3, Fig. S4, Fig. S5.
Case report
The proband, a 15-year-old girl from Yulin City, Guangxi, China was born normally and without any observable development delay. The proband was diagnosed with thalassemia (-SEA/αα; βCD17/βCD17:homozygote) in October 2002 at Yulin People's Hospital of Guangxi Province, China at 6 years of age and did not initially receive regular blood transfusion. By 10 years of age, she was admitted to a local hospital due to cold symptoms and received a blood transfusion for the first time. At 13 years and 8 months old, she had a Hb level of 55 g/l and received a transfusion of 4 units of leukocyte-poor red blood cells (LPRC), her second blood transfusion, and was subsequently discharged from the hospital. At 13 years and 9 months old, she presented at Shenzhen Second People's Hospital (Shenzhen, China), experiencing headaches and dizziness without obvious cause. She had a Hb level of 51 g/l and was admitted to hospital. At the time of admission, the proband weighed 33.9 kg, below the 3rd percentile. She exhibited facial characteristics of thalassemia (the skull was enlarged, the cheekbones prominent, the eye distance widened and the bridge of the nose was low and flat.), marked paleness and fatigue, but was not jaundiced. The proband's liver was 4 cm below the midclavicular line of the right costal margin, the spleen was 8 cm below the left costal margin and she had grade III ejection systolic murmurs at the apex.
On the day of her admission, routine hematological evaluation revealed a Hb level of 51 g/l, a mean corpuscular volume (MCV) of 69 fl, a mean corpuscular Hb (MCH) of 21.3 pg, a white blood cell (WBC) count of 8.83×109/l and a platelet count of 143×109/l. On day 2, her Hb further dropped to 37 g/l and she subsequently received a transfusion of 2 units of LPRC. Three days later, she remained fatigued and dizzy and continued to exhibit grade III ejection systolic murmurs at the apex. An echocardiogram showed that in the resting state, there was no obvious abnormality in the intracardiac structure and blood flow. As the proband's Hb level was 52 g/l, she received another transfusion of 2 units of LPRC. Five days after admission, she complained of dizziness in the morning with a Hb level of 66 g/l and received a third transfusion of 2 units of LPRC. Six days after admission, her Hb level recovered to 85 g/l and she received a fourth transfusion of 2 units of LPRC. Blood tests for total bilirubin, unconjugated bilirubin, aspartate aminotransferase, alanine aminotransferase, serum ferritin (FER), human growth hormone, triiodothyronine, total thyroid hormone, free triiodothyronine, free thyroid hormone, serum thyroid stimulating hormone, human chorionic gonadotropin, progesterone, estradiol and follicle-stimulating hormone were performed (Table II). Seven days after admission, T2*-weighted MRI analysis revealed moderate iron overload in the patients' liver. Notably, Hb electrophoresis showed changes of HbF fraction (normal range, <2.3%) and HbA2 fraction (normal range, 2.5-3.5%). The father showed an increased HbA2 fraction, with HbA (92.79%; lane 6), HbF (1.32%; lane 7) and HbA2 (5.89%; lane 11). The probands mother showed increased HbF compared to the father with HbA (89.89%; lane 6), HbF (7.54%; lane 7) and HbA2 (2.56 %; lane 11), and the proband exhibited HbA (82.45%; lane 6), HbF (14.78%; lane 7) and HbA2 (2.78%; lane 11) (Fig. 2). Hematological data of the family showed changes of Hb (normal range, 110–150 g/l), MCV (normal range, 80–100 fl) and MCH (normal range, 27–34 pg) The proband showed data on fluctuations. The father and mother showed both MCV and MCH decreased (Table III).
Since several studies have reported that Chinese Gγ+(Aγδβ)°-thalassemia is clinically manifested as no anemia or mild anemia, with increased HbF (10–18%), and normal Hb A2 (2.5-3.5%) (16,17), it was suspected that the proband may carry Chinese Gγ+(Aγδβ)°-thalassemia, and therefore the genotypes of the girl and her parents were analyzed using gap-PCR, PCR-RDB and MLPA (Fig. S6, Fig. S7). The common-SEA deletion and Chinese Gγ+(Aγδβ)°-thalassemia were detected using gap-PCR and the codon17(A>T)(HBB: c.52A>T) mutation was detected by PCR-RDB. The data showed that the father was heterozygous for the codon17(A>T)(HBB: c.52A>T; Fig. 3C), the mother carried the Chinese Gγ+(Aγδβ)°-thalassemia combined with the-SEA deletion in a double heterozygous state and no point mutations of HBB were detected by PCR-RDB (Fig. 3A and B, respectively; Fig. S8, and their daughter inherited both mutations from her mother and father, thus carrying the Chinese Gγ+(Aγδβ)°/βCD17-thalassemia combined with the-SEA deletion in a compound heterozygous state (Fig. 3; Table IV). Ten days later, the proband had occasional dizziness. Her Hb level was 96 g/l and hematological indexes were significantly improved. The proband received a total of eight LPRC transfusions over 10 days, with Hb fluctuating between 37–96 g/l. The patient's hematological indexes are summarized in Table IV.
Since the diagnosis of the Chinese Gγ+(Aγδβ)°/βCD17-thalassemia combined with the-SEA deletion at 13 years and 10 months old, the proband became transfusion dependent. She has since received four units per month of LPRCs in view of her low Hb level and persistent symptoms. Her Hb level remained a steady 90–105 g/l throughout the following 18 months, prior to follow-up. FER levels were regularly screened during follow-up and iron-chelating therapy, desferrioxamine mesylate, was administered when FER was >1,000 ng/ml. Liver and kidney function was monitored periodically by clinical biochemical analysis. The proband, now 15 years and 3 months old is still under regular follow-up at the Department of Hematology of Shenzhen Second People's Hospital (Shenzhen, China), and is progressing well. Towards the start of patient follow-up, the Hb level dropped to 62 g/l, and stabilized between 90–105 g/l in the middle to late stages. WBCs were consistently maintained within the biological reference interval, whereas MCV and MCH were consistently below the biological reference interval. RBC gradually rises towards the biological reference range, indicates that the anemia symptoms are not further aggravated. These results during follow-up are displayed in Fig. 4. A timeline of the probands disease progression is shown in Fig. 5.
Discussion
Thalassemia is a hereditary hemolytic disease that is prevalent in Southeast Asia, the Indian subcontinent, and Africa. In China, there is a high incidence of α-thalassemia in Guangdong is 8.53% and β-thalassemia is 2.54% (18). The large population base and high carrying rate result in various types of thalassemia. In 1972, Chinese Gγ+(Aγδβ)°-thalassemia was first reported by Mann et al (11), the deletion range of which involves Aγ, ψβ, δ, β-alleles and 3′-HS-1 regions of globin gene cluster, covering ~100 kb (7). This mutation is generated through non-homologous recombination (5). Although a number of previous studies have reported that the clinical manifestations of Chinese Gγ+(Aγδβ)°-thalassemia heterozygotes show significantly reduced MCV and MCH levels, it is a typical characteristic of mild thalassemia with microcytic hypochromic anemia (12–14,19,20). However, when Chinese Gγ+(Aγδβ)°-thalassemia coexists with other common β-thalassemia gene mutations, the patients often exhibit moderate or severe anemia with increased HbF levels (12–14).
To date, there are few studies reporting a compound heterozygous mutation of Chinese Gγ+(Aγδβ)°/βN-thalassemia combined with α-thalassemia (21). In a previous study, the Chinese Gγ+(Aγδβ)°/βCD41-42-thalassemia combined with the-α3.7 deletions was reported to be transfusion independent (13). In the present report, the proband had no obvious disease symptoms before 13 years of age in 2020. After a severe, unexplained headache and dizziness, hepatosplenomegaly and marked paleness and fatigue were discovered at 13 years and 9 months old and the hematological results (Hb, 51 g/l; MCV, 69 fl; MCH, 21.3 pg) lead to the diagnosis of β-thalassemia intermedia. As headache and dizziness cannot be relieved by clinical treatment, Hb has been reduced to 37 g/l, which can only be treated by regular blood transfusion. The Hb level returned to normal, increased to 90–105 g/l and remained stable for ~18 months.
Intermediate thalassemia patients vary in degree of anemia, the severity of onset is closely related to the amount of β-chain synthesis, most symptoms in childhood, the clinical manifestations of moderate anemia between mild and severe, mild or moderate spleen enlargement, may have jaundice, varying degrees of skeletal changes, sexual development delay. There is a wide range of variation among individuals with different intermediate forms of β-thalassemia: in mild cases, clinical symptoms are not significant, and physical examination reveals small cell hypothermic anemia and moderate hemoglobin reduction. In severe cases, similar to severe beta-thalassemia, the liver and spleen are enlarged and require irregular blood transfusion to maintain life (21–23). The present study highlighted a case of Chinese Gγ+(Aγδβ)°/βCD17-thalassemia combined with an -SEA deletion, an uncommon β-thalassemia state (transitioning to severe β-thalassemia state with age) caused by a rare β-globin genotype.
In the present report, analysis of the proband's peripheral blood samples revealed βCD17 locus mutation homozygous thalassemia combined with the-SEA deletion. Her father presents with βCD17 locus mutation thalassemia, and the mother presents with-SEA deletion mutation thalassemia. As the proband's HbF value of 14.78% was significantly elevated, she and her mother were subjected to further genetic tests and were found to carry the Chinese Gγ+(Aγδβ)°-thalassemia mutation. The present findings suggested that when genetic tests of thalassemia are found to be homozygous and further pedigree analysis does not support this result, the possibility of the presence of a Chinese Gγ+(Aγδβ)°-thalassemia deletion gene should be considered; that is, the impression of ‘homozygosity’ in the presence of a large segment of another chromosome gene deletion results in wrong judgments. Within the Chinese population, Gγ+(Aγδβ)°-thalassemia and South-East Asian-type hereditary persistent fetal hemoglobinemia are the most common causes of significantly increased HbF levels (≥10%) (16). Therefore, for cases with increased HbF levels, the aforementioned deletions should be analyzed first, and MLPA can be used to detect other types of β-globin gene deletions when necessary. If the conventional thalassemia gene tests reveal a homozygous state for the mutation site and this result does not match clinical symptoms or thalassemia screening results, deletion of the β-globin gene cluster should be considered. In the present case, the proband was accurately diagnosed with the rare Chinese Gγ+(Aγδβ)°/βCD17 and the-SEA deletion genotype. In clinical practice, the diagnosis of a thalassemia gene is based on the diagnostic principle of combining phenotype and genotype. When the hematologic phenotype of the subject is inconsistent with the genotype of thalassemia detected by routine tests, rare or undiscovered mutations may exist, which should be further tested and analyzed for confirmation. The results of this case also confirmed the importance and practicability of this genetic diagnosis principle for thalassemia.
The present case report is a textbook model for β-thalassemia, outlining both the clinical and the genetical heterogeneity of the disease, as well as the importance of age-related complications. Complications of β-thalassemia intermedia are associated with ineffective hematopoietic bone marrow, chronic anemia and progressive iron overload. Symptoms usually start between 6–10 years of age and increase in severity with age. Timely blood transfusion and iron removal treatment can delay and reduce the occurrence of childhood complications.
The molecular diagnosis of β-thalassemia in light of the clinical progression of the disease should be carefully discussed. The differences between β-thalassemia intermedia and β-thalassemia major are usually difficult to distinguish; however, according to the proband's blood transfusion requirements outlined in the present report (average pre-transfusion Hb level <60 g/l) the most reasonable diagnosis is severe thalassemia intermedia.
Supplementary Material
Supporting Data
Acknowledgements
Not applicable.
Funding
The work was supported by Shenzhen High-level Hospital Construction Fund and by a grant from the Shenzhen Science and Technology Innovation Commission (grant. no. JCYJ20170817172241688).
Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Authors' contributions
HQ, WLL and WFL designed the present study. XHL, XLZ, JX, WHZ and YW performed the experiments and analyzed the data. HQ wrote the manuscript. HQ and WLL confirm the authenticity of all the raw data. All authors read and approved the final version of the manuscript.
Ethics approval and consent to participate
The study protocol was conducted in line with The Declaration of Helsinki, and was approved by the Ethics Committee of Shenzhen Second People's Hospital (Shenzhen, China; approval no. 20210707004); written informed consent was obtained from the parents for themselves and on behalf of the patient.
Patient consent for publication
Written informed consent was obtained from the parents of the patient.
Competing interests
The authors declare that they have no competing interests.
Glossary
Abbreviations
Abbreviations:
|
MCH |
mean corpuscular hemoglobin |
|
MCV |
mean corpuscular volume |
|
MLPA |
multiplex ligation-dependent probe amplification |
|
PLT |
platelet count |
|
PCR-RDB |
PCR-reverse dot-blot hybridization |
|
WBC |
white blood cell |
References
|
Martin A and Thompson AA: Thalassemias. Pediatr Clin North Am. 60:1383–1391. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
He S, Li J, Li DM, Yi S, Lu X, Luo Y, Liang Y, Feng C, Chen B, Zheng C and Qiu X: Molecular characterization of α- and β-thalassemia in the Yulin region of Southern China. Gene. 655:61–64. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Cao A and Galanello R: Beta-thalassemia. Genet Med. 12:61–76. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Galanello R, Sanna S, Perseu L, Sollaino MC, Satta S, Lai ME, Barella S, Uda M, Usala G, Abecasis GR and Cao A: Amelioration of Sardinian beta0 thalassemia by genetic modifiers. Blood. 114:3935–3937. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Panyasai S, Fucharoen S, Surapot S, Fucharoen G and Sanchaisuriya K: Molecular basis and hematologic characterization of deltabeta-thalassemia and hereditary persistence of fetal hemoglobin in Thailand. Haematologica. 89:777–781. 2004.PubMed/NCBI | |
|
Zeng YT, Huang SZ, Chen B, Liang YC, Chang ZM, Harano T and Huisman TH: Hereditary persistence of fetal hemoglobin or (delta beta)o-thalassemia: three types observed in South-Chinese families. Blood. 66:1430–1435. 1985. View Article : Google Scholar : PubMed/NCBI | |
|
Chen W, Zhang X, Shang X, Cai R, Li L, Zhou T, Sun M, Xiong F and Xu X: The molecular basis of beta-thalassemia intermedia in southern China: Genotypic heterogeneity and phenotypic diversity. BMC Med Genet. 11:312010. View Article : Google Scholar : PubMed/NCBI | |
|
So CC, So AC, Chan AY, Tsang ST, Ma ES and Chan LC: Detection and characterisation of beta-globin gene cluster deletions in Chinese using multiplex ligation-dependent probe amplification. J Clin Pathol. 62:1107–1111. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang JW, Song WF, Zhao YJ, Wu GY, Qiu ZM, Wang FN, Chen SS and Stamatoyannopoulos G: Molecular characterization of a novel form of (A gamma delta beta)zero thalassemia deletion in a Chinese family. Blood. 81:1624–1629. 1993. View Article : Google Scholar : PubMed/NCBI | |
|
Zhuang J, Jiang Y, Wang Y, Zheng Y, Zhuang Q, Wang J and Zeng S: Molecular analysis of α-thalassemia and β-thalassemia in Quanzhou region Southeast China. J Clin Pathol. 73:278–282. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Mann JR, MacNeish AS, Bannister D, Clegg JB, Wood WG and Weatherall DJ: δβ-thalassemia in a chinese famiIy. Br J Haematol. 23:393–402. 1972. View Article : Google Scholar : PubMed/NCBI | |
|
Peng CT, Liu SC, Chiou SS, Kuo PL, Shih MC, Chang JY and Chang JG: Molecular characterization of deletional forms of beta-thalassemia in Taiwan. Ann Hematol. 82:33–36. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Tan Jin Ai MA, Yap SF, Tan KL, Wong YC, Wee YC and Kok JL: Mild beta-thalassemia intermedia caused by compound heterozygosity for (G)gamma((A)gammadeltabeta)(o)/beta-thalassemia and molecular characterization of the defect in four Chinese families. Acta Haematol. 109:169–175. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Wu Y, Yao Q, Zhong M, Wu J, Xie L, Su L and Yu F: Genetic research and clinical analysis of deletional Chinese Gγ+(Aγδβ)°-thalassemia and Southeast Asian HPFH in South China. Ann Hematol. 99:2747–2753. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
He S, Wei Y, Lin L, Chen Q, Yi S, Zuo Y, Wei H, Zheng C, Chen B and Qiu X: The prevalence and molecular characterization of (δβ)° -thalassemia and hereditary persistence of fetal hemoglobin in the Chinese Zhuang population. J Clin Lab Anal. 32:e223042018. View Article : Google Scholar : PubMed/NCBI | |
|
Cai WJ, Li J, Xie XM and Li DZ: Screening for common β-globin gene cluster deletions in Chinese individuals with increased hemoglobin F. Int J Lab Hematol. 37:752–757. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Craig JE, Barnetson RA, Prior J, Raven JL and Thein SL: Rapid detection of deletions causing delta beta thalassemia and hereditary persistence of fetal hemoglobin by enzymatic amplification. Blood. 83:1673–1682. 1994. View Article : Google Scholar : PubMed/NCBI | |
|
Xu XM, Zhou YQ, Luo GX, Liao C, Zhou M, Chen PY, Lu JP, Jia SQ, Xiao GF, Shen X, et al: The prevalence and spectrum of alpha and beta thalassaemia in Guangdong Province: Implications for the future health burden and population screening. J Clin Pathol. 57:517–522. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Du L, QD, Wang JC, et al: Analysis and prenatal diagnosis of 5 families with 813-thalassemia. J Mol Diagn Ther. 7:27–32. 2015. | |
|
Chen M, Zhang M, Chen L, Lin N, Wang Y, Xu L and Huang H: Genetic research and clinical analysis of β-globin gene cluster deletions in the Chinese population of Fujian province: A 14-year single-center experience. J Clin Lab Anal. 36:e241812022.PubMed/NCBI | |
|
Liang HF, Liang WM, Xie WG, Lin F, Liu LL, Li LJ, Ge YY, Lu M, Liao YW, Zeng GK, et al: The gene spectrum of thalassemia in Yangjiang of western Guangdong Province. Front Genet. 14:11260992023. View Article : Google Scholar : PubMed/NCBI | |
|
Taher AT, Radwan A and Viprakasit V: When to consider transfusion therapy for patients with non-transfusion-dependent thalassaemia. Vox Sang. 108:1–10. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Weatherall DJ: The definition and epidemiology of non-transfusion-dependent thalassemia. Blood Rev. 26 (Suppl 1):S3–S6. 2012. View Article : Google Scholar : PubMed/NCBI |
