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Hematology (Amsterdam, Netherlands) Dec 2023In China, conventional genetic testing methods can only detect common thalassemia variants. Accurate detection of rare thalassemia is crucial for clinical diagnosis,...
BACKGROUND
In China, conventional genetic testing methods can only detect common thalassemia variants. Accurate detection of rare thalassemia is crucial for clinical diagnosis, especially for children that need long-term blood transfusion. This study aims to explore the application value of third-generation sequencing (TGS) in the diagnosis of rare thalassemia in children with anemia.
METHODS
We enrolled 20 children with anemia, excluding from iron deficiency anemia (IDA). TGS was employed to identify both known and novel thalassemia genotypes, while sanger sequencing was used to confirm the novel mutation detected.
RESULTS
Among the 20 samples, we identified 5 cases of rare thalassemia. These included β (hg38,Chr11:5226187-5231089) at gene, α(:c.*91delT), α(:c.91-93delGAG), Chinese γ(γδβ)(NG_000007.3: g .48795-127698 del 78904) and delta (:c.-127T>C). Notably, the -/αα genotype associated with severe non-deletional hemoglobin H disease (HbH disease) has not been previously reported. Patients with genotypes β/β and -/αα necessitate long-term blood transfusions, and those with the -/αα, Chinese γ(γδβ) and delta thalassemia demonstrate mild anemia.
CONCLUSIONS
TGS demonstrates promising potential as a diagnostic tool for suspected cases of rare thalassemia in children, especially those suspected to have transfusion-dependent thalassemia (TDT).
Topics: Child; Humans; alpha-Thalassemia; Anemia; Asian People; beta-Thalassemia; China; Genotype; Hemoglobins; High-Throughput Nucleotide Sequencing; Mutation; Rare Diseases; Thalassemia; Blood Transfusion
PubMed: 37548329
DOI: 10.1080/16078454.2023.2241226 -
British Journal of Haematology Oct 2022In the not so distant past, pregnancy in thalassaemia patients was considered a very high risk and often not recommended. The results regarding alpha-thalassaemia and in...
In the not so distant past, pregnancy in thalassaemia patients was considered a very high risk and often not recommended. The results regarding alpha-thalassaemia and in particular haemoglobin H disease by Srimeuniwai and colleagues are very encouraging. Nowadays thalassaemic women not only become pregnant, but maternal outcome is not decreased compared to controls. Commentary on: Ake-sittipaisarn, et al. Outcomes of pregnancies complicated by haemoglobin H-Constant Spring and deletional haemoglobin H disease: A retrospective cohort study. Br J Haematol 2022;199:122-129.
Topics: Female; Hemoglobin H; Humans; Pregnancy; Retrospective Studies; alpha-Thalassemia
PubMed: 35968718
DOI: 10.1111/bjh.18362 -
Medicine Mar 2022There is no information concerning the prevalence of thalassemia among pregnant women in Hubei Province currently. This study is aimed to explore the prevalence of α-... (Observational Study)
Observational Study
There is no information concerning the prevalence of thalassemia among pregnant women in Hubei Province currently. This study is aimed to explore the prevalence of α- and β-thalassemia genotypes among pregnant women in Hubei Province, and to explore the clinically applicable screening approach, as well as to investigate the pregnancy outcomes of α- and β-thalassemia carriers.Pregnant participants were recruited from 4 hospitals for the screening of α- and β-thalassemia mutations in Hubei Province. Polymerase Chain Reaction and flow cytometry methods were used to examine α- and β-thalassemia mutations. The hematological parameters and pregnancy outcomes of α- and β-thalassemia carriers were obtained from the hospital information system. The chi-square tests were used to evaluate the difference in hematological parameters between pregnant thalassemia carriers and the control group.Among 11,875 participants, 414 (3.49%) were confirmed with α-thalassemia carriers, 228 (1.92%) were confirmed with β-thalassemia carriers, and 3 (0.03%) were confirmed with both α- and β-thalassemia carriers. The frequency of -α3.7 accounted for 2.05% and it was the most frequent genotype of α-thalassemia; the proportion of IVS-II-654 was 0.85% and it was the most frequent genotype of β-thalassemia in Hubei Province. Furthermore, the proportion of patients with low mean corpuscular volume (MCV) or mean cell hemoglobin (MCH) values was accounted for 36.64% and 93.97% among α-thalassemia and β-thalassemia carriers, respectively. And participants with normal MCV and MCH values were accounted for 95.07% among non-thalassemia participants. High prevalence of pregnancy-induced diabetes (16.97%), preterm birth (9.96%), pregnancy-induced hypertension (8.12%), and low birth weight (5.90%) were observed among pregnant thalassemia carriers.MCV and MCH values were suggested to apply on the preliminary screening of pregnant β-thalassemia; however, it's unpractical on that of α-thalassemia. Furthermore, thalassemia carriers might have a high risk of negative pregnancy outcomes. These findings could be useful for the preliminary screening of thalassemia and perinatal care for the pregnant thalassemia carriers.
Topics: China; Diabetes, Gestational; Female; Genotype; Hemoglobins; Humans; Hypertension, Pregnancy-Induced; Infant, Low Birth Weight; Infant, Newborn; Male; Polymerase Chain Reaction; Pregnancy; Pregnancy Complications, Hematologic; Pregnant Women; Premature Birth; Prevalence; alpha-Thalassemia; beta-Thalassemia
PubMed: 35244037
DOI: 10.1097/MD.0000000000028790 -
International Journal of Molecular... Mar 2023Extracellular vesicles (EVs) are nano-scaled vesicles released from all cell types into extracellular fluids and specifically contain signature molecules of the original... (Review)
Review
Extracellular vesicles (EVs) are nano-scaled vesicles released from all cell types into extracellular fluids and specifically contain signature molecules of the original cells and tissues, including the placenta. Placenta-derived EVs can be detected in maternal circulation at as early as six weeks of gestation, and their release can be triggered by the oxygen level and glucose concentration. Placental-associated complications such as preeclampsia, fetal growth restriction, and gestational diabetes have alterations in placenta-derived EVs in maternal plasma, and this can be used as a liquid biopsy for the diagnosis, prediction, and monitoring of such pregnancy complications. Alpha-thalassemia major ("homozygous alpha-thalassemia-1") or hemoglobin Bart's disease is the most severe form of thalassemia disease, and this condition is lethal for the fetus. Women with Bart's hydrops fetalis demonstrate signs of placental hypoxia and placentomegaly, thereby placenta-derived EVs provide an opportunity for a non-invasive liquid biopsy of this lethal condition. In this article, we introduced clinical features and current diagnostic markers of Bart's hydrops fetalis, extensively summarize the characteristics and biology of placenta-derived EVs, and discuss the challenges and opportunities of placenta-derived EVs as part of diagnostic tests for placental complications focusing on Bart's hydrop fetalis.
Topics: Female; Pregnancy; Humans; alpha-Thalassemia; Hydrops Fetalis; Placenta; Hemoglobins, Abnormal; Extracellular Vesicles; Prenatal Diagnosis
PubMed: 36982732
DOI: 10.3390/ijms24065658 -
Clinical and Applied... 2022About 2% of the population in the world are carriers of the thalassemia gene. Thalassemia is highly prevalent in Southern China, and traditional clinical testing... (Review)
Review
About 2% of the population in the world are carriers of the thalassemia gene. Thalassemia is highly prevalent in Southern China, and traditional clinical testing methods would cause missed diagnosis of partial static thalassemia. Here, we reviewed and summarized a set of simple and clinically feasible thalassemia detection protocols adopted by the Prenatal Diagnosis and Reproductive Center of our hospital. From January 1, 2015, to December 31, 2020, 31 512 peripheral blood samples and 3828 prenatal samples were collected in our study. All the peripheral blood samples were performed through thalassemia screening by routine blood tests and hemoglobin electrophoresis and gene detection. The prenatal diagnosis would be implemented for the fetus if the parents were carriers of the same type of thalassemia. A total of 6137 (19.48%) cases were diagnosed as thalassemia, in which 4749 (15.07%) were α-thalassemia, 1196 (3.80%) were β-thalassemia and 192 (0.61%) were co-inheritance of α- and β-thalassemia. For prenatal samples, 3160 (82.55%) cases were diagnosed as thalassemia, in which 2021 (52.80%) were α-thalassemia, 997 (26.05%) were β-thalassemia and 142 (3.71%) were co-inheritance of α- and β-thalassemia. In addition, we also found five novel mutations, including NC_000016.9:g.223681-227492del3812; HBA1: c.301-31_301-24delCTCGGCCCinsG; HBA2: c.95+7C>T for α-thalassemia and HBB: c.263_276delCACTGAGTGAGCTG; HBB: c.315+143G>A for β-thalassemia. The present study updates the epidemiological characteristics and mutation spectrum of thalassemia in Southern China and demonstrated five novel mutations. Our research provides a reference for clinical diagnosis and treatment, prenatal diagnosis, or reproductive genetic counseling for patients with thalassemia in Guangdong.
Topics: China; Female; Genotype; Humans; Molecular Epidemiology; Mutation; Pregnancy; Prenatal Diagnosis; alpha-Thalassemia; beta-Thalassemia
PubMed: 35979587
DOI: 10.1177/10760296221119807 -
Biomedical and Environmental Sciences :... Oct 2021Thalassemia is a group of genetically heterogeneous diseases characterized by hemolytic anemia. To investigate molecular characteristics of α- and β-thalassemia among...
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 -- deletion was the highest in α-thalassemia (66.01%), followed by -α (17.98%) and -α (8.22%), and the frequency of CD41-42 (-TCTT) mutation was the highest in β-thalassemia (38.38%), followed by IVS-II-654 (C > T) (25.67%), -28 (A > G) (15.76%), and CD17 (10.01%). In addition, 5 rare mutations (--THAI and HKαα, CD113, -90, and CD56) were found in the study population. Our results revealed molecular epidemiological background of α- and β-thalassemia in Guangdong Province, which can support optimization of thalassemia prevention and control strategies. We demonstrated that thalassemia is heterogeneous with significant geographical differences and population specificity.
Topics: Adult; China; Female; Genotype; Humans; Male; Middle Aged; Mutation; Sequence Analysis, DNA; Young Adult; alpha-Thalassemia; beta-Thalassemia
PubMed: 34782049
DOI: 10.3967/bes2021.112 -
International Journal of Laboratory... Jun 2023Hemoglobin disorders are among the most common genetic diseases worldwide. Molecular diagnosis is helpful in cases where the diagnosis is uncertain and for genetic... (Review)
Review
Hemoglobin disorders are among the most common genetic diseases worldwide. Molecular diagnosis is helpful in cases where the diagnosis is uncertain and for genetic counseling. Protein-based diagnostic techniques are frequently adequate for initial diagnosis. Molecular genetic testing is pursued in some cases, particularly when a definitive diagnosis is not possible and especially for the purpose of assessing genetic risk for couples wanting to have children. The expertise available in the clinical hematology laboratory is essential for the diagnosis of patients with hemoglobin abnormalities. Initial diagnoses are made using protein-based techniques such as electrophoresis and chromatography. Based on these findings, genetic risk to an individual's offspring can be assessed. In the setting of β-thalassemia and other β-globin disorders, coincident α-thalassemia may be difficult to diagnose, which can have potentially serious consequences. In addition, unusual forms of β-thalassemia caused by deletions in the β-globin locus cannot be definitively characterized using standard techniques. Molecular diagnostic testing has an important role in the diagnosis of hemoglobin disorders and is important in the setting of genetic counseling. Molecular testing also has a role in prenatal diagnosis to identify fetuses affected by severe hemoglobinopathies and thalassemias.
Topics: Pregnancy; Female; Child; Humans; beta-Thalassemia; Hemoglobinopathies; alpha-Thalassemia; Prenatal Diagnosis; Molecular Diagnostic Techniques; beta-Globins
PubMed: 37211360
DOI: 10.1111/ijlh.14089 -
Zhongguo Shi Yan Xue Ye Xue Za Zhi Jun 2023To investigate the possible causes of abnormal hemoglobin electrophoresis results.
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.
Topics: Humans; Female; Pregnancy; beta-Thalassemia; Anemia, Iron-Deficiency; Fetal Hemoglobin; alpha-Thalassemia; Blood Protein Electrophoresis; Hemoglobin A2; Hemoglobins, Abnormal
PubMed: 37356947
DOI: 10.19746/j.cnki.issn.1009-2137.2023.03.031 -
BMC Nephrology Aug 2020Cardiorenal syndrome (CRS), a serious condition with high morbidity and mortality, is characterized by the coexistence of cardiac abnormality and renal dysfunction....
BACKGROUND
Cardiorenal syndrome (CRS), a serious condition with high morbidity and mortality, is characterized by the coexistence of cardiac abnormality and renal dysfunction. There is limited information about CRS in association thalassemia. This study aimed to investigate the prevalence of CRS in thalassemia patients and also associated risk factors.
METHODS
Thalassemia patients who attended the out-patient clinic of a tertiary care university hospital from October 2016 to September 2017 were enrolled onto this cross-sectional study. Clinical and laboratory findings from 2 consecutive visits, 3 months apart, were assessed. The criteria for diagnosis of CRS was based on a system proposed by Ronco and McCullough. Cardiac abnormalities are assessed by clinical presentation, establishment of acute or chronic heart failure using definitions from 2016 ESC guidelines or from structural abnormalities shown in an echocardiogram. Renal dysfunction was defined as chronic kidney disease according to the 2012 KDIGO guidelines.
RESULTS
Out of 90 thalassemia patients, 25 (27.8%) had CRS. The multivariable analysis showed a significant association between CRS and extramedullary hematopoiesis (EMH) (odds ratio (OR) 20.55, p = 0.016); thalassemia type [β/β vs β/β thalassemia (OR 0.005, p = 0.002)]; pulmonary hypertension (OR 178.1, p = 0.001); elevated serum NT-proBNP (OR 1.028, p = 0.022), and elevated 24-h urine magnesium (OR 1.913, p = 0.016). There was no association found between CRS and frequency of blood transfusion, serum ferritin, liver iron concentration, cardiac T2*, type of iron chelating agents, or urine neutrophil gelatinase-associated lipocalin level.
CONCLUSIONS
CRS is relatively common in thalassemia patients. Its occurrence is associated with laboratory parameters which are easily measured in clinical practice.
Topics: Adolescent; Adult; Blood Transfusion; Cardio-Renal Syndrome; Female; Hematopoiesis, Extramedullary; Humans; Hypertension, Pulmonary; Iron Chelating Agents; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Young Adult; alpha-Thalassemia; beta-Thalassemia
PubMed: 32746879
DOI: 10.1186/s12882-020-01990-8 -
Hemoglobin Nov 2023α-Thalassemia (α-thal) is a globally prevalent genetic disorder of hemoglobin (Hb) structure where the rate of α-globin chain synthesis is reduced or absent due to...
α-Thalassemia (α-thal) is a globally prevalent genetic disorder of hemoglobin (Hb) structure where the rate of α-globin chain synthesis is reduced or absent due to the presence of α-globin mutation(s). The aim of this study is to define the spectrum of α-globin gene mutations and evaluate their allele frequency in a group of α-thal carriers. A total of 55 individuals with possible α-thal patients were referred from the thalassemia centers in Syria. They have unexplained hypochromia and microcytosis. All patients were genetically tested for 21 common α-globin gene mutations using reverse hybridization kit. Seven different α-globin gene mutations and 13 different genotypes were detected in 55 patients. The two most frequently encountered mutations were -α deletion (47.1%) and -- mutation (21.4%). The most commonly observed genotype was -α/αα (40%), followed by --/αα genotype (21.8%). We determined the most common α thalassemia mutations in the Syrian patients. α-Thalassemia mutations with deletions were mostly observed in our study.
Topics: Humans; alpha-Thalassemia; Syria; Mutation; Genotype; Hemoglobins; alpha-Globins
PubMed: 38146675
DOI: 10.1080/03630269.2023.2296927