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Frontiers in Pediatrics 2023To explore the genotypes and allele frequencies of α, β and α+β thalassemias in Li minorities, which resided in Hainan Province of China for a long time.
PURPOSE
To explore the genotypes and allele frequencies of α, β and α+β thalassemias in Li minorities, which resided in Hainan Province of China for a long time.
METHODS
In the present study, 1,438 newborns of the Li minority were collected from January 2020 to April 2021. The genotypes of thalassemia were detected by fluorescence PCR and verified by flow-through hybridization PCR analyses. Rare genotypes were detected by restriction fragment length polymorphism electrophoresis and Sanger DNA sequencing.
RESULTS
Among 1,438 participants, 1,024 (71.2%) were diagnosed with any kind of thalassemia. Among all thalassemia carriers, 902 (88.09%) subjects were diagnosed with α-thalassemia, and 18 subtypes of α-thalassemia were detected, with the top three genotypes being -α/αα (25.39%), -α/αα (22.62%) and αα/αα (16.96%). Thirty-two (3.13%) patients were β-thalassemia carriers, and 6 types of β-thalassemia genotypes were detected. The top two genotypes were β/β (46.88%) and β/β (18.75%). Additionally, 90 (8.79%) cases were α + β-thalassemia, and the top two genotypes were -α/αα, β/β (30.00%) and -α/αα, β/β (26.67%). Furthermore, two genotypes (-α/HKαα and β/β) were first identified in Hainan Province and β/β was first identified in China.
CONCLUSION
Newborns of Li have a higher prevalence of thalassemia for a long period, and further education on the impact of thalassemia, follow-up studies of the clinical manifestation and treatment and proper intervention methods should be designed to reduce the burden of thalassemia and enhance the quality of life in Li newborns.
PubMed: 37020650
DOI: 10.3389/fped.2023.1139387 -
Scientific Reports Aug 2022α-Thalassemia is a common inherited blood disorder manifested mainly by the deletions of α-globin genes. In geographical areas with high carrier frequencies, screening...
α-Thalassemia is a common inherited blood disorder manifested mainly by the deletions of α-globin genes. In geographical areas with high carrier frequencies, screening of α-thalassemia carrier state is therefore of vital importance. This study presents a novel method for identifying female carriers of common α-thalassemia deletions using samples routinely taken for non-invasive prenatal tests for screening of fetal chromosomal aneuploidies. A total of 68,885 Vietnamese pregnant women were recruited and α-thalassemia statuses were determined by gap-PCR, revealing 5344 women (7.76%) carried deletions including αα/-- (4.066%), αα/-α (2.934%), αα/-α (0.656%), and rare genotypes (0.102%). A two-stage model was built to predict these α-thalassemia deletions from targeted sequencing of the HBA gene cluster on maternal cfDNA. Our method achieved F1-scores of 97.14-99.55% for detecting the three common genotypes and 94.74% for detecting rare genotypes (-α/-α, αα/--, -α/--, -α/--). Additionally, the positive predictive values were 100.00% for αα/αα, 99.29% for αα/--, 94.87% for αα/-α, and 96.51% for αα/-α; and the negative predictive values were 97.63%, 99.99%, 99.99%, and 100.00%, respectively. As NIPT is increasingly adopted for pregnant women, utilizing cfDNA from NIPT to detect maternal carriers of common α-thalassemia deletions will be cost-effective and expand the benefits of NIPT.
Topics: Cell-Free Nucleic Acids; China; Female; Genotype; Humans; Mutation; Polymerase Chain Reaction; Pregnancy; alpha-Globins; alpha-Thalassemia; beta-Thalassemia
PubMed: 35945425
DOI: 10.1038/s41598-022-17718-7 -
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 -
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 -
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 -
Indian Journal of Hematology & Blood... Apr 2022Carriers of α-thalassemia exhibit hypochromic microcytosis with mean corpuscular volume (MCV) < 80 fL, mean corpuscular hemoglobin (MCH) < 27 pg, and reduced...
Carriers of α-thalassemia exhibit hypochromic microcytosis with mean corpuscular volume (MCV) < 80 fL, mean corpuscular hemoglobin (MCH) < 27 pg, and reduced hemoglobin A (HbA). We studied the distribution and diagnostic efficiencies of these indicators and their combinations in patients with and without alpha-thalassemia. Based on genetic diagnosis, 10,883 participants were divided into alpha-thalassemia group (n = 1655) and negative-for-alpha-thalassemia group (n = 9228). Erythrocyte parameters and hemoglobin analysis of the groups were analyzed. Moreover, we compared the four screening schemes (MCV/MCH, MCV/MCH/HbA, MCV + MCH, MCV + MCH + HbA) to find the best for α-thalassemia screening. The genotypes of --/αα, and -α/αα are the most prevalent with 54.9% and 27.6% in Fujian Province, China. There were significant differences in the distribution of MCV, MCH, and HbA in the two groups. Among the three, MCH exhibited the highest sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy. Although the four screening schemes have their advantages, there are significant differences in their sensitivity and specificity. MCV + MCH had the best diagnostic performance (72.6% sensitivity, 89.0% specificity) as well as the highest Youden index (61.59%). Our results showed that MCH could be used to screen α-thalassemia instead of MCV and HbA. However, it is recommended that MCV/MCH/HbA screening be used in areas with high α-thalassemia incidence to increased sensitivity.
PubMed: 35496953
DOI: 10.1007/s12288-021-01449-2 -
The Journal of Nutrition Dec 2018The relation between subclinical hemoglobinopathies and concentrations of the iron-regulatory hormone hepcidin is not well characterized.
BACKGROUND
The relation between subclinical hemoglobinopathies and concentrations of the iron-regulatory hormone hepcidin is not well characterized.
OBJECTIVE
We investigated the relation of hepcidin concentration with hemoglobinopathies among young children in Kenya.
METHODS
We quantified serum hepcidin and ferritin in 435 Kenyan children aged 14-20 mo in a subsample of the Water, Sanitation, and Handwashing (WASH) Benefits Trial. Blood samples were genotyped for α+-thalassemia and for sickle cell disorder. Hepcidin was compared across sickle cell and α+-thalassemia genotypes separately by using generalized linear models, and children who were normozygous for both conditions were also compared with those who had either of these conditions. In the association between hepcidin and ferritin, we assessed effect modification by genotype.
RESULTS
In this population, we found that 16.2% had sickle cell trait and 0.2% had sickle cell disorder, whereas 40.0% were heterozygous for α+-thalassemia and 8.2% were homozygous. Hepcidin concentration did not differ by genotype, but effect modification was found by genotype in the association between hepcidin and ferritin (P < 0.1). Among normozygous sickle cell children (HbAA), there was an association between hepcidin and ferritin (β = 0.92; 95% CI: 0.72, 1.10). However, among those with sickle cell trait (HbAS), the association was no longer significant (β = 0.31; 95% CI: -0.04, 0.66). Similarly, among children who were normozygous (αα/αα) or heterozygous (-α/αα) for α+-thalassemia, hepcidin and ferritin were significantly associated [β = 0.94 (95% CI: 0.68, 1.20) and β = 0.77 (95% CI: 0.51, 1.03), respectively]; however, in children who were homozygous for α+-thalassemia (-α/-α), there was no longer a significant association (β = 0.45; 95% CI: -0.10, 1.00).
CONCLUSION
Hepcidin was not associated with hemoglobin genotype, but there may be a difference in the way hepcidin responds to iron status among those with either sickle cell trait or homozygous α+-thalassemia in young Kenyan children. This trial was registered at clinicaltrials.gov as NCT01704105.
Topics: Anemia, Sickle Cell; Child, Preschool; Female; Ferritins; Hemoglobin A; Hepcidins; Humans; Infant; Male; alpha-Thalassemia
PubMed: 30517728
DOI: 10.1093/jn/nxy229 -
International Journal of Environmental... Oct 2020Alpha(α)-thalassemia is a blood disorder caused by many types of inheritable α-globin gene mutations which causes no-to-severe clinical symptoms, such as Hb Bart's... (Meta-Analysis)
Meta-Analysis
Alpha(α)-thalassemia is a blood disorder caused by many types of inheritable α-globin gene mutations which causes no-to-severe clinical symptoms, such as Hb Bart's hydrops fetalis that leads to early foetal death. Therefore, the aim of this meta-analysis was to provide an update from year 2010 to 2020 on the prevalence of α-thalassemia in Southeast Asia. A systematic literature search was performed using PubMed and SCOPUS databases for related studies published from 2010 to 2020, based on specified inclusion and exclusion criteria. Heterogeneity of included studies was examined with the I2 index and Q-test. Funnel plots and Egger's tests were performed in order to determine publication bias in this meta-analysis. Twenty-nine studies with 83,674 subjects were included and pooled prevalence rates in this meta-analysis were calculated using random effect models based on high observed heterogeneity (I2 > 99.5, -value < 0.1). Overall, the prevalence of α-thalassemia is 22.6%. The highest α-thalassemia prevalence was observed in Vietnam (51.5%) followed by Cambodia (39.5%), Laos (26.8%), Thailand (20.1%), and Malaysia (17.3%). No publication bias was detected. Conclusions: This meta-analysis suggested that a high prevalence of α-thalassemia occurred in selected Southeast Asia countries. This meta-analysis data are useful for designing thalassemia screening programs and improve the disease management.
Topics: Asia, Southeastern; Humans; Prevalence; alpha-Thalassemia
PubMed: 33050119
DOI: 10.3390/ijerph17207354 -
Advances in Hematology 2020Alpha-thalassemia is highly prevalent in the plural society of Brazil and is a public health problem. There is limited knowledge on its accurate frequency and...
Alpha-thalassemia is highly prevalent in the plural society of Brazil and is a public health problem. There is limited knowledge on its accurate frequency and distribution in the Amazon region. Knowing the frequency of thalassemia and the prevalence of responsible mutations is, therefore, an important step in the understanding and control program. Hematological and molecular data, in addition to serum iron and serum ferritin, from 989 unrelated first-time blood donors from Amazonas Hemotherapy and Hematology Foundation (FHEMOAM) were collected. In this study, the subjects were screened for - /, - -, and - deletions. Alpha-thalassemia screening was carried out between 2016 and 2017 among 714 (72.1%) male and 275 (27.9%) female donors. The aims of this analysis were to describe the distribution of various alpha-thalassemia alleles by gender, along with their genotypic interactions, and to illustrate the hematological changes associated with each phenotype. Amongst the patients, 5.35% ( = 53) were diagnosed with deletion - and only one donor with deletion. From the individuals with - , 85.8% ( = 46) were heterozygous and 14.20% ( = 7) were homozygous. The frequency of the - deletion was higher in male (5.89%) than in female (4.0%). There is no significant difference in the distribution of - by gender ( = 0.217). The - , -, and - deletions were not found. All subjects were analyzed for serum iron and serum ferritin, with 1.04% being iron deficient ( = 5) and none with very high levels of stored iron (>220 g/dL). Alpha-thalassemia-2 deletion was the most common allele detected in Manaus blood donors, which is a consistent result, once it is the most common type of -thalassemia found throughout the world. As expected, the mean of hematological data was significantly lower in alpha-thalassemia carriers ( < 0.001), mainly homozygous genotype. Leukocytes and platelet count did not differ significantly. Due to the small number of individuals with iron deficiency found among blood donors, the differential diagnosis between the two types of anemia was not possible, even because minor changes were found among hematological parameters with iron deficiency and -thalassemia. Despite this, the study showed the values of hematological parameters, especially MCV and MCH, are lower in donors with iron deficiency, especially when associated with -thalassemia, and therefore, it may be useful to discriminate different types of microcytic anaemia. In conclusion, we believed screening for thalassemia trait should be included as part of a standard blood testing before blood donation. It should be noted that this was the first study to perform the screening for alpha deletions in blood donors from the Manaus region, and further studies are required to look at the effects of donated thalassemic blood.
PubMed: 32351571
DOI: 10.1155/2020/4170259