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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 -
Journal of Clinical Pathology May 2020Thalassemia is one of the most prevalent inherited disorders in south China. However, there still has no comprehensive research on molecular characterisation of...
AIMS
Thalassemia is one of the most prevalent inherited disorders in south China. However, there still has no comprehensive research on molecular characterisation of α-thalassemia and β-thalassemia in the Quanzhou region of Fujian province, a city with high incidence of thalassemia in Southeast China.
METHODS
A total of 11 668 cases were collected in Quanzhou region from January 2013 to June 2019. The deletions of α-thalassemia were detected by Gap-PCR, α-thalassemia and β-thalassemia mutations were detected by DNA reverse dot blot hybridisation. Rare thalassemia gene testing and DNA sequencing were performed to detect rare and novel thalassemia mutation for suspected rare thalassemia carriers.
RESULTS
Among 11 668 subjects, 4796 (41.10%) subjects were diagnosed with thalassemia. 3298 (28.27%) subjects were α-thalassemia carriers, 26 types of α-thalassemia mutations were identified, with the common α-thalassemia genotypes being --/αα (71.47%), -α/αα (17.13%) and -α/αα (3.49%). 1407 (12.06%) subjects were β-thalassemia carriers, 18 types of β-thalassemia mutations were identified. The common five genotypes of β-thalassemia were β/β (36.53%), β/β (30.28%), β/β (17.13%), β/β (5.12%) and β/β (4.62%). Additionally, 91 (0.78%) subjects with composite α-thalassemia and β-thalassemia were identified. Furthermore, 9 α-thalassemia and β-thalassemia gene mutations (CAP +40-43 (-AAAC), IVS-I-1 (G>T), IVS-I-5 (G>C), SEA-HPFH, CD53 (-T), CD37 (A>G), -90 (C>T), CD3 (T>C), -α) were identified for the first time in the region. Among them, CD53 (-T), CD37 (A>G) and -90 (C>T) mutations were identified for the first time in Fujian province. Moreover, CD3 (T>C), -α mutations were first identified in Chinese individual.
CONCLUSIONS
Quanzhou region of South China has high incidence of thalassemia mutations. In this study, several cases of rare thalassemia mutations have been identified, providing reference for clinical consultation. The completion of this study is of great significance to strengthen the prevention and control of thalassaemia in the Quanzhou region.
Topics: Adolescent; Adult; China; Female; Genetic Markers; Genotype; Humans; Male; Middle Aged; Mutation; Prevalence; Sequence Analysis, DNA; Young Adult; alpha-Thalassemia; beta-Thalassemia
PubMed: 31653757
DOI: 10.1136/jclinpath-2019-206179 -
BioMed Research International 2019Unlike the other hemoglobinopathies, few researches have been published concerning -thalassemia in Morocco. The epidemiological features and the mutation spectrum of...
Unlike the other hemoglobinopathies, few researches have been published concerning -thalassemia in Morocco. The epidemiological features and the mutation spectrum of this disease are still unknown. This regional newborn screening is the first to study -thalassemia in the north of Morocco. During the period from January 2015 to December 2016, 1658 newborns umbilical blood samples were investigated. Suspected newborns were screened for -globin defects using Gap-PCR and Multiplex Ligation-dependent Probe Amplification technique. The prevalence of -thalassemia, its mutation spectrum, and its allelic frequencies were described for the first time in Morocco. Six different -globin genetic disorders were detected in 16 neonates. This screening valued the prevalence of -thalassemia in the studied population at 0.96% and showed the wide mutation spectrum and the heterogeneous geographical distribution of the disease. A high rate of carriers was observed in Laouamra, a rural commune in Larache province. Heterogeneity of -globin alleles in Morocco explains the high variability of -thalassemia severity. This diversity reflects the anthropological history of the country. These results would contribute to the prevention of thalassemia in Morocco directing the design of a nationwide screening strategy and awareness campaign.
Topics: Alleles; Female; Gene Frequency; Humans; Infant, Newborn; Male; Morocco; Mutation; Prevalence; alpha-Globins; alpha-Thalassemia
PubMed: 31001551
DOI: 10.1155/2019/2080352 -
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 -
MMWR. Morbidity and Mortality Weekly... Sep 2020Alpha-thalassemia comprises a group of inherited disorders in which alpha-hemoglobin chain production is reduced. Depending on the genotype, alpha-thalassemia results in...
Alpha-thalassemia comprises a group of inherited disorders in which alpha-hemoglobin chain production is reduced. Depending on the genotype, alpha-thalassemia results in moderate to profound anemia, hemolysis, growth delays, splenomegaly, and increased risk for thromboembolic events; certain patients might require chronic transfusions. Although alpha-thalassemia is not a core condition of the United States Recommended Uniform Screening Panel* for state newborn screening programs, methodologies used by some newborn screening programs to detect sickle cell disease, which is a core panel condition, also detect a quantitative marker of alpha-thalassemia, hemoglobin (Hb) Bart's, an abnormal type of hemoglobin. The percentage of Hb Bart's detected correlates with alpha-thalassemia severity. The Association of Public Health Laboratories' Hemoglobinopathy Workgroup conducted a survey of state newborn screening programs' alpha-thalassemia screening methodologies and reporting and follow-up practices. Survey findings indicated that 41 of 44 responding programs (93%) report some form of alpha-thalassemia results and 57% used a two-method screening protocol. However, the percentage of Hb Bart's used for thalassemia classification, the types of alpha-thalassemia reported, and the recipients of this information varied widely. These survey findings highlight the opportunity for newborn screening programs to revisit their policies as they reevaluate their practices in light of the recently released guideline from the Clinical and Laboratory Standards Institute (CLSI) on Newborn Screening for Hemoglobinopathies (1). Although deferring to local programs for policies, the report used a cutoff of 25% Hb Bart's in its decision tree, a value many programs do not use. Standardization of screening and reporting might lead to more timely diagnoses and health care services and improved outcomes for persons with a clinically significant alpha-thalassemia.
Topics: Female; Health Care Surveys; Humans; Infant, Newborn; Male; Neonatal Screening; United States; alpha-Thalassemia
PubMed: 32915167
DOI: 10.15585/mmwr.mm6936a7 -
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 -
International Journal of Hematology Sep 2021This study investigated prenatal diagnosis of α-thalassemia and β-thalassemia in 3049 families in 18 regions of Hainan Province. Molecular diagnosis was performed in...
This study investigated prenatal diagnosis of α-thalassemia and β-thalassemia in 3049 families in 18 regions of Hainan Province. Molecular diagnosis was performed in 3049 couples with thalassemia in Hainan Province. Genomic DNA was extracted from peripheral blood of the couples and villus, amniotic fluid, or cord blood of fetuses. DNA-based diagnosis was performed using polymerase chain reaction. The most commonly detected mutation for α-thalassemia was- SEA/αα (31.53%), followed by - α4.2/αα (11.15%) and - α3.7/αα (11.02%). The most common mutation for β-thalassemia was CD41/42 (30.27%), followed by - 28 (2.56%). Prevalence was highest in the coastal regions and lowest in the Wenchang, Lingao, and Ding'an regions. We also found that the most common gene mutations in Han people and other minority groups were not homogeneous. Prenatal diagnosis showed 556 normal fetuses, 116 with α-thalassemia hydrops, and 134 with β-thalassemia major. Our findings provide important information for clinical genetic counseling regarding prenatal diagnosis for thalassemia major in Hainan Province.
Topics: China; Female; Genotype; Geography, Medical; Heterozygote; Humans; Male; Mutation; Pregnancy; Prevalence; alpha-Globins; alpha-Thalassemia; beta-Globins; beta-Thalassemia
PubMed: 34195938
DOI: 10.1007/s12185-021-03173-z -
International Journal of Molecular... Jan 2023α-thalassemia is characterized in about 80% of cases by deletions generated by the presence of duplications and interspersed repeated sequences in the α-globin gene...
α-thalassemia is characterized in about 80% of cases by deletions generated by the presence of duplications and interspersed repeated sequences in the α-globin gene cluster. In a project on the molecular basis of α-thalassemia in Southern Italy, we identified six families, showing an absence of the most common deletions, and normal α-globin gene sequences. Multiplex Ligation-dependent Probe Amplification (MLPA), qRT-PCR, and the sequencing of long-range PCR amplicon have been used for the identification and characterization of new deletions. MLPA analysis for the identification of α- and β-globin rearrangement revealed the presence of five new α-thalassemia deletions. The set-up of qRT-PCR allowed us to delimit the extent of the deletions ranging from about 10 kb to more than 250 kb, two of them being of the telomeric type. The long-range PCR generated a specific anomalous fragment in three deletions, and only several unspecific bands in the other two deletions. The sequencing of the anomalous amplicons revealed the breakpoints of two deletions: the --PA, 34 kb long, identified in two families, and the telomeric --AG, 274 kb long. The anomalous fragment containing the breakpoint of the deletion --FG was partially sequenced, and it was not possible to identify the breakpoints due to the presence of several repetitive Alu sequences. The analysis of the breakpoint regions of the --Sciacca and --Puglia, respectively, are about 10 and 165 kb long, and revealed the presence of repeats that most likely impaired the amplification of a specific fragment for the identification of the breakpoint. MLPA, in association with qRT-PCR and long-range PCR, is a good approach for the identification and molecular characterization of rare or new deletions. Breakpoint analysis confirms that Alu sequences play an important role in favoring unequal crossing-over. Southern Italy shows considerable genetic heterogeneity, as expected with its central position in the Mediterranean basin, favoring migratory flows.
Topics: Humans; alpha-Thalassemia; alpha-Globins; Multigene Family; Multiplex Polymerase Chain Reaction; Italy
PubMed: 36768900
DOI: 10.3390/ijms24032577 -
Archives of Razi Institute Jun 2022The prevalence of alpha-thalassemia as a major health problem in the south of Iraq has highlighted the necessity of investigations and screening of patients with...
The prevalence of alpha-thalassemia as a major health problem in the south of Iraq has highlighted the necessity of investigations and screening of patients with thalassemia. The present study aimed to characterize the spectrum of alpha-globin gene mutations in patients who were followed up in a genetic diseases center in Thi-Qar province. A total of 30 subjects were collected from thalassemia patients and 15 cases as the control group. Polymerase chain reaction (PCR) and direct sequencing were performed for functionally regions of the gene (exon 1 and exon 2). The fragment size amplified was 442 bp in the Exon 1 region and 324 bp in the Exon 2 region of α-globin. The molecular analysis of the sequence of PCR products revealed that 13 point mutation within the α-thalassemia gene included deletion and substitution mutation, while the rest of the mutations were in the intron site of the gene. These results indicated that mutations may constitute a risk of developing hemophilia B disease. Molecular mechanisms in the expression of globin genes are used to help manage patients with thalassemia.
Topics: alpha-Globins; alpha-Thalassemia; Iraq; Mutation; Point Mutation; Humans
PubMed: 36618297
DOI: 10.22092/ARI.2022.357209.1997