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Journal of Clinical Laboratory Analysis Dec 2021Thalassemia is a group of inherited autosomal recessive hemolytic anemia disease caused by reduced or absent synthesis of globin chain/chains of hemoglobin. Only few... (Comparative Study)
Comparative Study
BACKGROUND
Thalassemia is a group of inherited autosomal recessive hemolytic anemia disease caused by reduced or absent synthesis of globin chain/chains of hemoglobin. Only few studies showed the molecular characterization of α- and β-thalassemia in Meizhou city of China.
METHODS
A total of 22,401 individuals were collected; hematological and hemoglobin electrophoresis analysis and thalassemia genetic testing were performed.
RESULTS
Eleven thousand and thirty (49.24%) cases with microcytosis (mean corpuscular volume (MCV) < 82 fl), 11,074 (49.44%) cases with hypochromia (mean corpuscular Hb (MCH) < 27 pg) in 22,401 subjects, 11,085 cases with abnormal hemoglobin results were identified in subjects aged ≥6 months. 7,322 (32.69%) subjects harbored thalassemia mutations, including 4,841 (21.61%) subjects with α-thalassemia, 2,237 (9.99%) with β-thalassemia, and 244 (1.09%) with α-thalassemia combined β-thalassemia. 18 genotypes of α-thalassemia mutations and 27 genotypes of β-thalassemia mutations were characterized. The most frequent α gene mutation was -- (64.69%), followed by -α (19.93%), -α (7.73%), α α (3.97%), and α α (2.83%). The six most common β-thalassemia mutations were IVS-II-654 (C>T) (39.79%), CD41-42 (-TCTT) (33.02%), -28 (A>G) (10.38%), CD17 (A>T) (9.08%), CD27-28 (+C) (2.14%), and CD26 (G>A) (2.02%). In addition, MCV and MCH were sensitive markers for α- and β-thalassemia except for -α /αα, -α /αα, α α/αα, α α/αα, and β /β .
CONCLUSIONS
The -- , -α , and -α deletions were the main mutations of α-thalassemia, while IVS-II-654 (C>T), CD41-42 (-TCTT), -28 (A>G), and CD17 (A>T) mutations of β-thalassemia in Meizhou. There were some differences in thalassemia mutation frequencies in Meizhou city from other populations in China.
Topics: Asian People; China; Cities; Erythrocyte Indices; Gene Frequency; Genotype; Hemoglobins; Humans; Mutation; Mutation Rate; alpha-Thalassemia; beta-Thalassemia
PubMed: 34752669
DOI: 10.1002/jcla.24105 -
Scientific Reports Jun 2022Thalassemia is a group of common hereditary anemias that cause significant morbidity and mortality worldwide. However, precisely diagnosing thalassemia, especially rare...
Thalassemia is a group of common hereditary anemias that cause significant morbidity and mortality worldwide. However, precisely diagnosing thalassemia, especially rare thalassemia variants, is still challenging. Long-range PCR and long-molecule sequencing on the PacBio Sequel II platform utilized in this study could cover the entire HBA1, HBA2 and HBB genes, enabling the diagnosis of most of the common and rare types of thalassemia variants. In this study, 100 cases of suspected thalassemia were subjected to traditional thalassemia testing and third-generation sequencing for thalassemia genetic diagnosis. Compared with traditional diagnostic methods, an additional 10 cases of rare clinically significant variants, including 3 cases of structure variants and 7 cases of single nucleotide variations (SNVs) were identified, of which a case with - α subtype III (- α) was first identified and validated in the Chinese population. Other rare variants of 11.1 kb deletions (- 11.1/αα), triplicate α-globin genes (aaa/αα) and rare SNVs have also been thoroughly detected. The results showed that rare thalassemia variants are not rare but have been misdiagnosed by conventional methods. The results further validated third-generation sequencing as a promising method for rare thalassemia genetic testing.
Topics: Genotype; Humans; Mutation; Sequence Analysis, DNA; alpha-Globins; alpha-Thalassemia; beta-Thalassemia
PubMed: 35701592
DOI: 10.1038/s41598-022-14038-8 -
Journal of Clinical Laboratory Analysis Mar 2022Hainan has one of the high incidences of thalassemia in China, but the epidemiological data in the whole province has not been reported yet. The objective of our study...
BACKGROUND
Hainan has one of the high incidences of thalassemia in China, but the epidemiological data in the whole province has not been reported yet. The objective of our study was to reveal the true prevalence and molecular mutation spectrum of thalassemia in the population of Hainan who are of childbearing age.
METHODS
We screened 166,936 individuals from 19 cities and counties in Hainan by hematological parameters analysis, and further conducted genetic analysis for individuals whose MCV was less than 82fL.
RESULTS
In total, 21,619 (12.95%) subjects were diagnosed as thalassemia carriers or patients. The overall prevalence of α-thalassemia, β-thalassemia, and α+β-thalassemia were 10.39%, 1.38%, and 1.18%, respectively. Eleven α-thalassemia mutations and sixteen β-thalassemia mutations were identified. The high-frequent genotypes of α-thalassemia were -α /αα (19.70%), -α /αα (19.39%), αα/-- (15.60%), α α/αα (9.24%), and -α /-α (8.90%), and those of β-thalassemia were β /β (58.92%), β /β (16.05%), β /β (8.42%), β /β (6.03%), β /β (5.47%), and β /β (2.69%). In addition, the frequencies and hematological profiles of many rare mutations of α- [Fusion, HKαα, αααanti , IVS-II-55 (T>G), IVS-II-119 (-G,+CTCGGCCC)] and β-globin genes [-50 (G>A), IVS-Ⅱ-81 (C>T)] in Hainan were reported for the first time.
CONCLUSION
Our study revealed the high prevalence and extensive molecular spectrum of thalassemia in childbearing age population of Hainan, suggesting thalassemia in Hainan ranks second in prevalence among all regions in China. The findings will be useful for genetic counseling and prevention of thalassemia.
Topics: China; Genotype; Heterozygote; Humans; Mutation; Prevalence; alpha-Thalassemia; beta-Thalassemia
PubMed: 35119136
DOI: 10.1002/jcla.24260 -
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 -
Journal of the American Heart... Apr 2017Recent studies have discovered that α-globin is expressed in blood vessel walls where it plays a role in regulating vascular tone. We tested the hypothesis that blood...
BACKGROUND
Recent studies have discovered that α-globin is expressed in blood vessel walls where it plays a role in regulating vascular tone. We tested the hypothesis that blood pressure (BP) might differ between normal individuals and those with αthalassemia, in whom the production of α-globin is reduced.
METHODS AND RESULTS
The study was conducted in Nairobi, Kenya, among 938 adolescents aged 11 to 17 years. Twenty-four-hour ambulatory BP monitoring and arterial stiffness measurements were performed using an arteriograph device. We genotyped for αthalassemia by polymerase chain reaction. Complete data for analysis were available for 623 subjects; 223 (36%) were heterozygous (-α/αα) and 47 (8%) were homozygous (-α/-α) for αthalassemia whereas the remaining 353 (55%) were normal (αα/αα). Mean 24-hour systolic BP ±SD was 118±12 mm Hg in αα/αα, 117±11 mm Hg in -α/αα, and 118±11 mm Hg in -α/-α subjects, respectively. Mean 24-hour diastolic BP ±SD in these groups was 64±8, 63±7, and 65±8 mm Hg, respectively. Mean pulse wave velocity (PWV)±SD was 7±0.8, 7±0.8, and 7±0.7 ms, respectively. No differences were observed in PWV and any of the 24-hour ambulatory BP monitoring-derived measures between those with and without αthalassemia.
CONCLUSIONS
These data suggest that the presence of αthalassemia does not affect BP and/or arterial stiffness in Kenyan adolescents.
Topics: Adolescent; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Case-Control Studies; Child; Cross-Sectional Studies; Female; Humans; Kenya; Male; Pulse Wave Analysis; Vascular Stiffness; alpha-Thalassemia
PubMed: 28381468
DOI: 10.1161/JAHA.117.005613 -
Journal of Epidemiology and Global... Dec 2018This prospective study assessed the prevalence and genetic analysis of - and -thalassemia and sickle cell anemia (SCA) in Southwest Iran. Hematological indices were...
This prospective study assessed the prevalence and genetic analysis of - and -thalassemia and sickle cell anemia (SCA) in Southwest Iran. Hematological indices were measured in 17,581 couples living in Khuzestan Province, Southwest Iran. Individuals with mean corpuscular volume <80, mean corpuscular hemoglobin <27, hemoglobin A2 ≥3/5 were considered as -thalassemia traits. Prevalence of minor -thalassemia, -thalassemia, SCA, iron deficiency anemia, and silent thalassemia were respectively identified in 995 (5.6%), 1169 (6.65%), 1240 (7.05%), 911 (5.18%), and 1134 (6.45%) individuals using a multiplex amplification refractory mutation system, and direct DNA sequencing of globin genes. Three codons IVS-II-1 (G → A; 26%; = 13), IVS-I-1 (G → T; 16%; = 8), and IVS-I-110 (G → A; 14%; = 7) were the most frequent mutants and IVS-II-1 was the most common -thalassemia mutation. Also, based on a gap-polymerase chain reaction assay, genotype frequencies of -globin mutations were - (50%; = 25), Med/ (12%; = 6), and -4.2/ (10%; = 5), which were the most frequent deletion mutants (72% in total). The most common deletion (50%) was -. Our data suggest that the population of Southwest Iran is at high risk of - and -thalassemia caused by these deletion mutants and SCA. Our findings will be useful for developing an efficient control program and genetic counseling.
Topics: Adult; Anemia, Sickle Cell; Erythrocyte Indices; Female; Genetic Testing; Humans; Iran; Male; Prevalence; Prospective Studies; Sequence Deletion; alpha-Globins; alpha-Thalassemia; beta-Thalassemia
PubMed: 30864762
DOI: 10.2991/j.jegh.2018.04.103 -
TheScientificWorldJournal Jul 2009Genetic mutations of the alpha genes are common worldwide. In Asia and particularly Southeast Asia, they can result in clinically significant types of alpha-thalassemia,... (Review)
Review
Genetic mutations of the alpha genes are common worldwide. In Asia and particularly Southeast Asia, they can result in clinically significant types of alpha-thalassemia, namely hemoglobin (Hb) H disease and Hb Bart's hydrops fetalis. The latter is generally a fatal intrauterine condition, while Hb H disease results in clinical complications that are frequently overlooked. The high prevalence of the carrier state and the burden of these diseases (and other alpha-thalassemia variants) call for more attention for improved screening methods and better care.
Topics: Genetic Carrier Screening; Genetic Testing; Genotype; Humans; Infant, Newborn; Neonatal Screening; Phenotype; Syndrome; alpha-Thalassemia
PubMed: 19618088
DOI: 10.1100/tsw.2009.69 -
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 -
Journal of Clinical Laboratory Analysis Nov 2016α-Thalassemia is a benign condition that is often present in patients with diabetes mellitus. Here, we evaluated the effects of different genotypes α-thalassemia on...
BACKGROUND
α-Thalassemia is a benign condition that is often present in patients with diabetes mellitus. Here, we evaluated the effects of different genotypes α-thalassemia on HbA measurement.
METHODS
A total of 189 samples from nondiabetic patients were analyzed. HbA analysis was performed by ion-exchange high-performance liquid chromatography, boronate affinity HPLC, immunoassay, and capillary electrophoresis. Fasting glucose, fructosamin, and HbA were also performed. All samples were confirmed by genotyping for thalassemia.
RESULTS
In patients with two or three functional α-genes, HbA values were not significantly different from those of controls (P > 0.05); however, in individuals with α-thalassemia with one functional α-gene (i.e., HbH disease), HbA levels were significantly different from those of controls (P < 0.01). HbA values were significantly lower in individuals with HbH disease than in control individuals and patients in the other two α-thalassemia groups. For patients with HbH disease, there were no significant differences in the four HbA measurement systems (P > 0.05).
CONCLUSIONS
In this study, HbA values in samples from individuals with two or three functional α-genes basically reflected the normal mean blood glucose level, while those in samples from individuals with one functional α-gene did not.
Topics: Adult; Chromatography, High Pressure Liquid; Fasting; Female; Ferritins; Fructosamine; Glycated Hemoglobin; Humans; Male; Young Adult; alpha-Thalassemia
PubMed: 27184351
DOI: 10.1002/jcla.21983 -
Genetic Testing and Molecular Biomarkers Jul 2017Thalassemia is a dangerous hematolytic genetic disease. In south China, ∼24% Chinese carry alpha-thalassemia or beta-thalassemia gene mutations. Given the fact that...
AIMS
Thalassemia is a dangerous hematolytic genetic disease. In south China, ∼24% Chinese carry alpha-thalassemia or beta-thalassemia gene mutations. Given the fact that the invasive sampling procedures can only be performed by professionals in experienced centers, it may increase the risk of miscarriage or infection. Thus, most people are worried about the invasive operation. As such, a noninvasive and accurate prenatal diagnosis is needed for appropriate genetic counseling for families with high risks. Here we sought to develop capture probes and their companion analysis methods for the noninvasive prenatal detection of deletional and nondeletional thalassemia.
MATERIALS AND METHODS
Two families diagnosed as carriers of either beta-thalassemia gene or Southeast Asian deletional alpha-thalassemia gene mutation were recruited. The maternal plasma and amniotic fluid were collected for prenatal diagnosis. Probes targeting exons of the genes of interest and the highly heterozygous SNPs within the 1Mb flanking region were designed. The target capture sequencing was performed with plasma DNA from the pregnant woman and genomic DNA from the couples and their children. Then the parental haplotype was constructed by the trios-based strategy. The fetal haplotype was deduced from the parental haplotype with a hidden Markov model-based algorithm.
RESULTS
The fetal genotypes were successfully deduced in both families noninvasively. The noninvasively constructed haplotypes of both fetuses were identical to the invasive prenatal diagnosis results with an accuracy rate of 100% in the target region.
CONCLUSION
Our study demonstrates that the effective noninvasive prenatal diagnosis of alpha-thalassemia and beta-thalassemia can be achieved with the targeted capture sequencing and the haplotype-assisted analysis method.
Topics: Adult; Amniotic Fluid; China; DNA; DNA Probes; Female; Fetus; Genetic Counseling; Genotype; Haplotypes; Humans; Pedigree; Pilot Projects; Polymorphism, Single Nucleotide; Pregnancy; Prenatal Diagnosis; Sequence Analysis, DNA; alpha-Thalassemia; beta-Thalassemia
PubMed: 28537755
DOI: 10.1089/gtmb.2016.0411