RESUMEN
BACKGROUND: New hemoglobin (Hb) variants are constantly being updated as assays are developed and the testing population expands. Here, we report a novel Hb variant, named Hb Guigang. METHODS: Hemoglobin (Hb) analysis was analyzed by capillary electrophoresis (CE) and high-performance liquid chromatography (HPLC). Glycated hemoglobin was performed by CE and HPLC. Routine genetic analysis was done with Gap-PCR and PCR-reverse dot-blot hybridization. The hemoglobin variant was identified by Sanger sequencing. RESULTS: CE of three cases showed the presence of Hb variants in Zone 5 and Zone 12, respectively. HPLC indicated an elevated P3 peak, suggesting the possible presence of the Hb variant. Hb A1c was measured by CE and HPLC, and the results were 6.7% and 4.76%, respectively. Sanger sequencing confirmed an AAGËAAT mutation at codon 90 of the HBA1 gene. This mutation was reported for the first time, and we named it Hb Guigang based on the proband's place of residence. CONCLUSIONS: Hb Guigang with normal hematological parameters was separated and quantified by CE, whereas HPLC suggested that Hb Guigang co-eluted with the P3 peaks and could not be quantified.
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Electroforesis Capilar , Hemoglobina Glucada , Hemoglobinas Anormales , Globinas alfa , Humanos , Hemoglobinas Anormales/genética , Globinas alfa/genética , Cromatografía Líquida de Alta Presión , Hemoglobina Glucada/análisis , Hemoglobina Glucada/metabolismo , Masculino , Femenino , Mutación , Análisis Mutacional de ADN , AdultoRESUMEN
ABSTRACT: ß-thalassemia is a condition characterized by reduced or absent synthesis of ß-globin resulting from genetic mutations, leading to expanded and ineffective erythropoiesis. Mitoxantrone has been widely used clinically as an antitumor agent considering its ability to inhibit cell proliferation. However, its therapeutic effect on expanded and ineffective erythropoiesis in ß-thalassemia is untested. We found that mitoxantrone decreased α-globin precipitates and ameliorated anemia, splenomegaly, and ineffective erythropoiesis in the HbbTh3/+ mouse model of ß-thalassemia intermedia. The partially reversed ineffective erythropoiesis is a consequence of effects on autophagy as mitochondrial retention and protein levels of mTOR, P62, and LC3 in reticulocytes decreased in mitoxantrone-treated HbbTh3/+ mice. These data provide significant preclinical evidence for targeting autophagy as a novel therapeutic approach for ß-thalassemia.
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Modelos Animales de Enfermedad , Eritropoyesis , Mitoxantrona , Talasemia beta , Animales , Talasemia beta/tratamiento farmacológico , Eritropoyesis/efectos de los fármacos , Ratones , Mitoxantrona/farmacología , Mitoxantrona/uso terapéutico , Autofagia/efectos de los fármacos , Globinas alfa/genética , Reticulocitos/efectos de los fármacos , Reticulocitos/metabolismoRESUMEN
OBJECTIVE: To perform molecular diagnosis and pedigree analysis for one case with α-thalassemia who does not conform to the genetic laws, and explore the effects of a newly discovered rare mutation (HBA2:c.*12G>A) on clinical phenotypes. METHODS: Blood samples of the proband and her family members were collected for blood routine analysis, and the hemoglobin components were analyzed by capillary electrophoresis. The common α- and ß-globin gene loci in Chinese population were detected by conventional techniques (Gap-PCR, RDB-PCR). The α-globin gene sequences (HBA1, HBA2) were analyzed by Sanger sequencing. RESULTS: By analyzing the test results of proband and her family members, the genotype of the proband was -α3.7/HBA2:c.*12G>A, her father was HBA2:c.*12G>A heterozygous mutation carrier. CONCLUSION: This study identifies a rare α-globin gene mutation (HBA2:c.*12G>A) that has not been reported before. It is found that heterozygous mutation carriers present with static α-thalassemia.
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Hemoglobina A2 , Globinas alfa , Talasemia alfa , Femenino , Humanos , Masculino , Globinas alfa/genética , Talasemia alfa/genética , Talasemia alfa/diagnóstico , Genotipo , Hemoglobina A2/genética , Heterocigoto , Mutación , Linaje , Fenotipo , Pueblos del Este de Asia/genéticaRESUMEN
OBJECTIVE: To analyze the gene mutation types and frequence of thalassemia patients in Jingzhou area. METHODS: A total of 721 suspected thalassemia patients who were visited in Jingzhou Central Hospital from June 2019 to June 2022 were selected as the research objects. There were 204 males and 517 females. PCR-reverse dot hybridization method was used to analyze the types and frequencies of 23 common α or ß thalassemia gene mutations. RESULTS: Among the 721 patients with suspected thalassemia, 228 cases were positive for α or ß thalassemia gene, with a total positive rate of 31.62%, including 87 cases of α-thalassemia, accounting for 38.16%, and 140 cases of ß-thalassemia, accounting for 61.40%. There was 1 case of α ß complex thalassemia, accounting for 0.44%. A total of 4 types of α-thalassemia gene mutations were detected, all of which were deletion types, including αα/--SEA (64/87, 73.56%), αα/-α3.7 (14/87, 16.09%), --SEA /-α3.7 (7/87, 8.05%), αα/-α4.2 (2/87, 2.30%). Among 140 patients with ß-thalassemia, 138 were pure heterozygotes, and the genotypes of IVS-II-654M (63/140, 45.00%), CD41-42M (34/140, 24.29%), CD17M (18/140, 12.86%) and CD27-28M (10/140, 7.14%) accounted for 89.29% of all mutations (125/140), 2 cases of double heterozygosity (2/140, 1.43%) were found, no homozygous ß-thalassemia were detected; 1 case of αß complex thalassemia with genotype -α3.7/IVS-II-654M was found. The incidence of difference types of thalassemia was statistically significant (χ2=194.250, P < 0.001). The percentage of positive thalassemia genes was not significantly difference between male and female suspected patients (χ2=0.199, P =0.655). CONCLUSION: The α-thalassemia gene mutation in Jingzhou area is dominated by αα/--SEA, and the IVS-II-654M mutation is more common in ß-thalassemia, and α ß complex thalassemia is relatively rare, which can provide a reference for the formulation of prevention and treatment measures for thalassemia in Jingzhou area.
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Mutación , Talasemia alfa , Talasemia beta , Humanos , Masculino , Femenino , Talasemia alfa/genética , Talasemia alfa/epidemiología , Talasemia beta/genética , Talasemia beta/epidemiología , China/epidemiología , Heterocigoto , Globinas alfa/genéticaAsunto(s)
Alelos , Heterocigoto , Fenotipo , Globinas alfa , Talasemia beta , Humanos , Talasemia beta/genética , Globinas alfa/genética , Masculino , Femenino , AdultoRESUMEN
α-thalassemia is a type of microcytic hypochromic anemia caused by variants of alpha-globin gene, and is one of the most common monogenic disorders in southern China. The population screening model based on hematologic phenotype has achieved great results in areas with high incidence of thalassemia. However, with the continuous decline of the cost of genetic testing and implementation of screening programs for thalassemia gene carriers, more variants in the alpha-globin gene have been discovered, which also brings great challenges to clinical genetic counseling. From the perspective of alpha-globin genetic analysis, this consensus has discussed the contents of pre- and post-test genetic counseling, with an aim to provide standardized guidance for clinicians.
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Asesoramiento Genético , Pruebas Genéticas , Talasemia alfa , Humanos , Talasemia alfa/genética , Talasemia alfa/diagnóstico , Globinas alfa/genética , ConsensoRESUMEN
Thalassemia is one of the most common and damaging monogenic diseases in the world. It is caused by pathogenic variants of α- and/or ß-globin genes, which disrupt the balance of these two protein chains and leads to α-thalassemia or ß-thalassemia, respectively. Patients with α-thalassemia or ß-thalassemia could exhibit a severe phenotype, with no simple and effective treatment. A three-tiered strategy of carrier screening, prenatal diagnosis and newborn screening has been established in China for the prevention and control of thalassemia, of which the first two parts have been studied thoroughly. The implementation of neonatal thalassemia screening is lagging, and the effectiveness of various screening programs has not yet been demonstrated. In this study, hemoglobin capillary electrophoresis (CE), hotspot testing method, and third-generation sequencing (TGS) were used in the variant detection of 2000 newborn samples, to assess the efficacy of these methods in neonatal thalassemia screening. Compared with CE (249, 12.45 %) and hotspot analysis (424, 21.2 %), CATSA detected the largest number of thalassemia variants (535, 26.75 %), which included 24 hotspot variants, increased copy number of α-globin gene, rare pathogenic variants, and three unreported potentially disease-causing variants. More importantly, CATSA directly determined the cis-trans relationship of variants in three newborns, which greatly shortens the clinical diagnosis time of thalassemia. CATSA showed a great advantage over other genetic tests and could become the most powerful technical support for the three-tiered prevention and control strategy of thalassemia.
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Alelos , Tamizaje Neonatal , Talasemia , Humanos , Recién Nacido , Talasemia/genética , Talasemia/diagnóstico , Electroforesis Capilar , Globinas alfa/genética , Secuenciación de Nucleótidos de Alto RendimientoRESUMEN
BACKGROUND Thalassemia and hemoglobin (Hb) variants are the most common hereditary red blood cell disorders worldwide. Alpha-thalassemia and alpha-globin variants are caused by mutations of the alpha-globin genes (HBA2 and HBA1), resulting in impaired alpha-globin production and structurally abnormal globin, respectively. Clinical severity of alpha-thalassemia correlates with the number of affected alpha-globin genes, yielding a spectrum of clinical manifestations from mild to severe anemia. Routine diagnosis involves Hb analysis and PCR-based methods, yet identifying rare variants necessitates comprehensive clinical and hematologic laboratory data. The knowledge of phenotype and genotype correlation is useful for genetic counseling and treatment planning. CASE REPORT A 59-year-old Thai woman presented with chronic anemia. Her baseline Hb level ranged between 8.0 and 9.0 g/dL, with no history of transfusion. Physical examination showed mild pallor, without enlarged liver and spleen. Laboratory investigations showed microcytic, hypochromic anemia and abnormal Hb peak by Hb analysis (retention time 4.58 min by HPLC method). Common alpha-globin gene deletions, including the Southeast-Asian/Thai 3.7 kb and 4.2 kb deletions were tested using gap-PCR, with none of these deletions detected. Direct DNA sequencing revealed a compound heterozygosity of Hb Jax (HBA2: c.44G>C) and Hb Constant Spring (HBA2: c.427T>C). CONCLUSIONS Compound heterozygosity of Hb Jax and Hb Constant Spring results in microcytic anemia. Hb Jax can be identified by Hb analysis, and diagnosis can be confirmed by direct DNA sequencing method. Coinheritance of Hb Jax and alpha-globin variants should be considered in cases with microcytic anemia and a specific Hb peak seen in Hb chromatogram.
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Anemia Hipocrómica , Hemoglobinas Anormales , Femenino , Humanos , Persona de Mediana Edad , Globinas alfa/genética , Talasemia alfa/genética , Talasemia alfa/diagnóstico , Anemia Hipocrómica/genética , Hemoglobinas Anormales/genéticaRESUMEN
BACKGROUND: The α-Major Regulatory Element (α-MRE), also known as HS-40, is located upstream of the α-globin gene cluster and has a crucial role in the long-range regulation of the α-globin gene expression. This enhancer is polymorphic and several haplotypes were identified in different populations, with haplotype D almost exclusively found in African populations. The purpose of this research was to identify the HS-40 haplotype associated with the 3.7 kb α-thalassemia deletion (-α3.7del) in the Portuguese population, and determine its ancestry and influence on patients' hematological phenotype. METHODS AND RESULTS: We selected 111 Portuguese individuals previously analyzed by Gap-PCR to detect the presence of the -α3.7del: 50 without the -α3.7del, 34 heterozygous and 27 homozygous for the -α3.7del. The HS-40 region was amplified by PCR followed by Sanger sequencing. Four HS-40 haplotypes were found (A to D). The distribution of HS-40 haplotypes and genotypes are significantly different between individuals with and without the -α3.7del, being haplotype D and genotype AD the most prevalent in patients with this deletion in homozygosity. Furthermore, multiple correspondence analysis revealed that individuals without the -α3.7del are grouped with other European populations, while samples with the -α3.7del are separated from these and found more closely related to the African population. CONCLUSION: This study revealed for the first time an association of the HS-40 haplotype D with the -α3.7del in the Portuguese population, and its likely African ancestry. These results may have clinical importance as in vitro analysis of haplotype D showed a decrease in its enhancer activity on α-globin gene.
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Haplotipos , Eliminación de Secuencia , Globinas alfa , Talasemia alfa , Femenino , Humanos , Masculino , Globinas alfa/genética , Talasemia alfa/genética , Población Negra/genética , Frecuencia de los Genes/genética , Genotipo , Haplotipos/genética , Portugal , Secuencias Reguladoras de Ácidos Nucleicos/genética , Eliminación de Secuencia/genéticaAsunto(s)
Eliminación de Secuencia , Talasemia alfa , Humanos , Talasemia alfa/genética , Brasil , Masculino , Globinas alfa/genética , Niño , Femenino , Hemoglobina H/genéticaRESUMEN
Alpha and Beta Thalassemia are autosomal recessive anemias that cause significant morbidity and mortality worldwide, especially in the Middle East and North Africa (MENA) region where carrier rates reach up to 50%. We report the case of two siblings of Palestinian origin born who presented to our tertiary healthcare center for the management of severe transfusion dependent hemolytic anemia. Before presentation to our center, the siblings were screened for a-thalassemia using the Alpha-globin StripAssay. They were found to carry the α2 polyA-1 [AATAAA > AATAAG] mutation in the heterozygous form, which was insufficient to make a diagnosis. No pathogenic variants were detected on Sanger sequencing of the HBB gene. Full sequencing of the a-gene revealed compound heterozygous variants (HBA1:c.119_121delCCA and the previously detected HBA2:c.*+94A > G Poly A [A->G]) with trans inheritance. This report highlights the impact of non-deletional mutations on α-globin chain stability. The compound heterozygosity of a rare α-globin chain pathogenic variant with a polyadenylation mutation in the probands leads to clinically severe a-thalassemia. Due to the high carrier status, the identification of rare mutations through routine screening techniques in our populations may be insufficient. Ongoing collaboration among hematologists, medical geneticists, and counselors is crucial for phenotypic-genotypic correlation and assessment of adequate genetic testing schemes.
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Hemoglobinas Anormales , Hermanos , Globinas alfa , Femenino , Humanos , Masculino , Globinas alfa/genética , Talasemia alfa/genética , Talasemia alfa/diagnóstico , Árabes/genética , Transfusión Sanguínea , Hemoglobinas Anormales/genética , Heterocigoto , Mutación , Preescolar , NiñoRESUMEN
The first identification of a novel α1-Globin variant, Hb Ormylia in 11 Greeks originating from a small village, Ormylia, Chalkidiki, Greece is reported. The new genetic variant leads to the production of a hemoglobin variant that can be identified and quantified by High-Performance Liquid Chromatography. Capillary and classic electrophoresis were not informative. Direct DNA sequencing revealed a new mutation C > G mutation at codon 21 of α1 gene (His > Gln). The new variant has been named Hb Ormylia and this is the first description of this genetic variant of α1 gene in the literature.
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Hemoglobinas Anormales , Globinas alfa , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Globinas alfa/genética , Talasemia alfa/genética , Talasemia alfa/diagnóstico , Sustitución de Aminoácidos , Grecia , Hemoglobinas Anormales/genética , MutaciónRESUMEN
OBJECTIVE: To analyze the mutations of globin genes among patients suspected for thalassemia from the Shanghai area. METHODS: A total of 4 644 patients diagnosed at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine between June 2016 and December 2019 were selected as the study subjects. The patients were tested for common mutations associated with thalassemia gene by Gap-PCR and reverse dot blotting (RDB). Patients were suspected to harbor rare mutations based on the inconsistency between hematological phenotypes and results of common mutation detection, and were further analyzed by Gap-PCR and Sanger sequencing. RESULTS: Among the 4 644 patients, 2 194 (47.24%) were found to carry common thalassemia mutations, among which 701 (15.09%) were α-thalassemia, 1 448 (31.18%) were ß-thalassemia, and 45 (0.97%) were both α- and ß-thalassemia. Forty six samples were found to harbor rare mutations, which included 17 α-globin gene and 29 ß-globin gene mutations. CD77(CCC>ACC) (HBA2: c.232C>A) of the α-globin gene, NG_000007.3: g.70567_71015del449, codon 102(-A) (HBB: c.308_308delA) and IVS-â ¡-636 (A>G) (HBB: c.316-215A>G) of the ß-globin gene were previously unreported new types of globin gene mutations. CONCLUSION: Among the 4 644 patients, the detection rate for common thalassemia mutations was 47.24%, whilst 46 samples were detected with rare gene mutations. The type of gene mutation types were diverse in the Shanghai area. The study has provided more accurate results for genetic diagnosis and counseling.
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Talasemia alfa , Talasemia beta , Humanos , Talasemia beta/genética , Talasemia beta/diagnóstico , Genotipo , Globinas beta/genética , China , Mutación , Talasemia alfa/genética , Globinas alfa/genéticaRESUMEN
OBJECTIVES: In clinical practice, the majority of α-thalassaemia cases arise from deletions of the α-globin genes. However, a subset of cases is attributed to rare haemoglobin variants, which can manifest with borderline or normal screening results, potentially leading to missed diagnoses in clinical practice. METHODS: Blood samples were collected from family members and underwent haematological, DNA and RNA analysis. RESULTS: The five-month-old proband presented a haematological phenotype consistent with Hb H disease. The mother's haematology profile was consistent with an α-thalassaemia carrier, while the father exhibited a borderline reduction in MCV and MCH. MALDI-TOF identified an abnormal α-chain in the proband. DNA analysis revealed a novel α-globin variant (HBA2:c.175C>A, α58His>Asn, Hb DG-Nancheng) affecting the distal histidine in the family. The father and the mother had α-genotype of --SEA/αα and αDG-Nanchengα/αα, respectively; while the proband inherited both mutant alleles (--SEA/αDG-Nanchengα). Sequencing of cDNA from HBA2 gene identified an equal ratio of normal and mutant alleles. CONCLUSION: This rare case highlighted the importance of identifying rare haemoglobin variant during prenatal screening. The clinical and genetic data provides useful information on the pathogenicity of this variant and further insight into the role of distal histidine residue of α-globin.
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Hemoglobinas Anormales , Talasemia alfa , Femenino , Humanos , Lactante , Embarazo , Globinas alfa/genética , Talasemia alfa/diagnóstico , Talasemia alfa/genética , China , Hemoglobinas Anormales/genética , Histidina/genética , MutaciónRESUMEN
In this short review, we presented and discussed studies on the expression of globin genes in ß-thalassemia, focusing on the impact of α-globin gene expression and α-globin modifiers on the phenotype and clinical severity of ß-thalassemia. We first discussed the impact of the excess of free α-globin on the phenotype of ß-thalassemia. We then reviewed studies focusing on the expression of α-globin-stabilizing protein (AHSP), as a potential strategy of counteracting the effects of the excess of free α-globin on erythroid cells. Alternative processes controlling α-globin excess were also considered, including the activation of autophagy by ß-thalassemia erythroid cells. Altogether, the studies reviewed herein are expected to have a potential impact on the management of patients with ß-thalassemia and other hemoglobinopathies for which reduction in α-globin excess is clinically beneficial.
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Hemoglobinopatías , Talasemia beta , Humanos , Talasemia beta/genética , Globinas alfa/genética , Globinas alfa/metabolismo , Hemoglobinopatías/genética , Fenotipo , Expresión Génica , Proteínas Sanguíneas/genética , Chaperonas Moleculares/genéticaRESUMEN
Patients with the genotype of ß0/ß0 for ß-thalassemia (ß-thal) usually behave as ß-thal major (ß-TM) phenotype which is transfusion-dependent. The pathophysiology of ß-thal is the imbalance between α/ß-globin chains. The degree of α/ß-globin imbalance can be reduced by the more effective synthesis of γ-globin chains, and increased Hb F levels, modifying clinical severity of ß-TM. We report a Chinese child who had homozygous ß0-thal and a heterozygous KLF1 mutation. The patient had a moderate anemia since 6 months old, keeping a baseline Hb value of 8.0-9.0 g/dL. She had normal development except for a short stature (3rd percentile) until 6 years old, when splenomegaly and facial bone deformities occurred. Although genetic alteration of KLF1 expression in ß0/ß0 patients can result in some degree of disease alleviation, our case shows that it is insufficient to ameliorate satisfactorily the presentation. This point should be borne in mind for physicians who provide the genetic counseling and prenatal diagnosis to at-risk families.
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Globinas beta , Talasemia beta , Niño , Femenino , Humanos , Lactante , Globinas alfa/genética , Globinas beta/genética , Talasemia beta/genética , China , Estudios de Seguimiento , Genotipo , MutaciónRESUMEN
We report a novel hemoglobin (Hb) variant found in a 34-year-old Chinese male during a routine measurement of glycated hemoglobin. The variant resulted in a P3 peak of 27.5% of the total Hb on high performance liquid chromatography (HPLC) with a glycated hemoglobin mode. However, no abnormal Hb peaks were observed in capillary electrophoresis (CE) with 3.1% Hb A2 and 96.9% Hb A. The amino acid substitution was determined by Sanger sequencing as α20 (B1) HisâLeu; the corresponding DNA mutation was identified as CAC > CTC at the first position of codon 20 of the α-chain. This is the first description of the mutation, and we have named it Hb Hebei for the region of origin of the proband.
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Hemoglobinas Anormales , Globinas alfa , Masculino , Humanos , Adulto , Hemoglobina Glucada/genética , Globinas alfa/genética , Mutación , Hemoglobinas Anormales/genética , Hemoglobinas Anormales/análisis , Sustitución de Aminoácidos , Cromatografía Líquida de Alta PresiónRESUMEN
OBJECTIVES: Accurate quantification of hemoglobin (Hb) A2 is vital for diagnosing ß-thalassemia carriers. This study aimed to assess the precision and diagnostic utility of HbA2 measurements using the new high-performance liquid chromatography (HPLC) method, Premier Resolution, in comparison to capillary electrophoresis (CE). METHODS: We analyzed 418 samples, previously identified as A2A by CE, using Premier Resolution-HPLC. We compared the results, established correlations, and determined an optimal HbA2 cutoff value for ß-thalassemia screening. Additionally, we prospectively evaluated the chosen cutoff value in 632 samples. Mutations in the ß- and α-globin genes were identified using polymerase chain reaction (PCR) techniques and DNA sequencing. RESULTS: HbA2 levels were consistently higher with Premier Resolution, yet there was a significant correlation with CE in all samples (bias, -0.33; r, 0.991), ß-thalassemia (bias, -0.27; r, 0.927), and non-ß-thalassemia carriers (bias, -0.36; r, 0.928). An HbA2 cutoff value of ≥4.0â¯% for ß-thalassemia screening achieved 100â¯% sensitivity and 99.6â¯% specificity. Further validation yielded sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 97.3â¯, 99.8, 97.3, 99.8, and 99.7â¯%, respectively. We also identified a rare ß-Hb variant, Hb La Desirade [HBB:c.389C>T], associated with ß-thalassemia and co-inherited with a single α-globin gene. CONCLUSIONS: The Premier Resolution HPLC is a reliable and accurate method for routine ß-thalassemia carrier screening, aligning with existing CE methods.
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Hemoglobina Falciforme , Talasemia beta , Humanos , Talasemia beta/diagnóstico , Talasemia beta/genética , Hemoglobina A/análisis , Reproducibilidad de los Resultados , Hemoglobina A2/genética , Hemoglobina A2/análisis , Mutación , Globinas alfa/genéticaRESUMEN
BACKGROUND: Thalassemia, a common autosomal hereditary blood disorder worldwide, mainly contains α- and ß-thalassemia. The α-globin gene triplicates allele is harmless for carriers, but aggravates the phenotype of ß-thalassemia. Therefore, it is particularly crucial to accurately detect the structural variants of α-globin gene clusters. CASE REPORT: We reported a 28-year-old man, the proband, with microcytic hypochromic anemia. From pedigree analysis, his mother and sister had hypochromic microcytosis, and his father was normal. Genetic testing of thalassemia identified a novel α-globin gene triplicate named αααanti4.2del726bp (NC_000016.10:g.170769_174300dupinsAAAAAA) by third-generation sequencing (TGS) in the proband and his father, which was further validated by multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing. The genotypes of the proband's mother and sister were both -α3.7/αα compounded with heterozygous HBB:c.126_129delCTTT. They were categorized as silent α-thalassemia with co-inheritance of ß-thalassemia trait. The proband's genotype additionally had the α-globin gene triplicates compared with his mother and sister, which increased the imbalance between α/ß-globin, so the proband had more severe hematological parameters. The proband's wife was diagnosed as HBA2:c.427T > C heterozygosis, and his daughter had the novel α-globin gene triplicates compounded with HBA2:c.427T > C, therefore the girl might be asymptomatic. CONCLUSION: The identification of the novel α-globin gene triplicates provides more insight for the research of thalassemia variants and indicates that TGS has signiï¬cant advantages on genetic testing of thalassemia for the reliability, accuracy and comprehensiveness.