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Human Genomics Aug 2023Thalassemia is an extremely prevalent monogenic inherited blood disorder in southern China. It is important to comprehensively understand the molecular spectrum of...
BACKGROUND
Thalassemia is an extremely prevalent monogenic inherited blood disorder in southern China. It is important to comprehensively understand the molecular spectrum of thalassemia in an area with such a high prevalence of thalassemia before taking appropriate actions for the prevention and treatment of this disorder. Herein, we explored the clinical feasibility of using next-generation sequencing (NGS) for large-scale population screening to illustrate the prevalence and spectrum of thalassemia in Southern Jiangxi.
METHODS
Blood samples collected from 136,312 residents of reproductive age in Southern Jiangxi were characterized for thalassemia by NGS. A retrospective analysis was then conducted on blood samples determined to be positive for thalassemia.
RESULTS
In total, 19,827 (14.545%) subjects were diagnosed as thalassemia carriers, and the thalassemia prevalence rate significantly varied by geographical region (p < 0.001). A total of 40 α-thalassemia genotypes including 21 rare genotypes were identified, with -@-/αα being the most prevalent genotype. 42 β-thalassemia genotypes including 27 rare genotypes were identified, with the most common mutation IVS II-654 C > T accounting for 35.257% of these β-thalassemia genotypes. Furthermore, 74 genotypes were identified among 608 individuals with combined α- and β-thalassemia. Notably, most individuals with rare thalassemia mutations had mildly abnormal hematologic parameters including microcytic hypochromia.
CONCLUSIONS
Our findings demonstrate the great heterogeneity and diverse spectrum of thalassemia in Southern Jiangxi, emphasizing the importance and necessity of persistent prevention and control of thalassemia in this region. Additionally, our findings further suggest that NGS can effectively identify rare mutations and reduce the misdiagnosis rate of thalassemia.
Topics: Humans; beta-Thalassemia; Retrospective Studies; alpha-Thalassemia; High-Throughput Nucleotide Sequencing; China
PubMed: 37592328
DOI: 10.1186/s40246-023-00520-5 -
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 -
Frontiers in Pharmacology 2014In utero hematopoietic cell transplantation (IUHCTx) is a promising strategy to circumvent the challenges of postnatal hematopoietic stem cell (HSC) transplantation. The... (Review)
Review
In utero hematopoietic cell transplantation (IUHCTx) is a promising strategy to circumvent the challenges of postnatal hematopoietic stem cell (HSC) transplantation. The goal of IUHCTx is to introduce donor cells into a naïve host prior to immune maturation, thereby inducing donor-specific tolerance. Thus, this technique has the potential of avoiding host myeloablative conditioning with cytotoxic agents. Over the past two decades, several attempts at IUHCTx have been made to cure numerous underlying congenital anomalies with limited success. In this review, we will briefly review the history of IUHCTx and give a perspective on alpha thalassemia major, one target disease for its clinical application.
PubMed: 25628564
DOI: 10.3389/fphar.2014.00278 -
Mediterranean Journal of Hematology and... 2022Sickle cell disease is a protean disease with limited data on Nigeria's phenotypic and genetic variants. This study was conducted to provide baseline data on these...
BACKGROUND
Sickle cell disease is a protean disease with limited data on Nigeria's phenotypic and genetic variants. This study was conducted to provide baseline data on these variants by characterising the existing forms of sickle cell disease and correlating these with basic haematological parameters.
METHODS
Adult and paediatric patients with SCD were recruited from a tertiary health centre in Nigeria. Patients were age and sex-matched with healthy controls. Blood samples were obtained for Full Blood Count, phenotyping by High-Performance Liquid Chromatography, and genotyping for alpha thalassemia by multiplex Gap-polymerase chain reaction. Data analysis was done using IBM SPSS statistics version 23.
RESULTS
A total of 130 patients with sickle cell disease and 117 controls were studied. Alpha thalassemia in the study population was due to a 3.7kb deletion in the alpha-globin gene cluster at a prevalence of 45.4% in the patients and 47% in the controls. The prevalence of the various existing forms of SCD genotype was: Homozygous S without alpha gene deletion (HbSS)- 39.2%; HbSC - 10.8%; HbSS- 35.4%; HbSS - 6.9% and HbSF- 7.7%. In the control population, HbAA without alpha gene deletion had a prevalence of 42.7%, HbAA was 25.6%, HbAA was 6%, HbAS- 7.7%, HbAS - 11.1%, HbAS - 2.6%, HbAC - 2.6% and HbAC - 1.7%. HbA was significantly elevated in HbSS individuals with two alpha gene deletions but reduced in normal controls (HbAA) with alpha gene deletions. HbF and HbA were negatively correlated with each other (r= -0.587, p < 0.001). Individuals with the HbSC genotype followed by HbSSα had the best haematological parameters.
CONCLUSIONS
Haematological parameters vary with haemoglobin genotype. The C haemoglobin and homozygous alpha-thalassemia deletion had a better ameliorating effect on SCD haematological parameters than the F haemoglobin in this population. The effect of alpha thalassemia on some haematological parameters in SCD patients are reversed in normal controls.
PubMed: 35070208
DOI: 10.4084/MJHID.2022.001 -
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 Clinical Laboratory Analysis Jun 2021Stroke is a devastating complication of sickle cell anemia (SCA) and can be predicted through abnormally high cerebral blood flow velocity using transcranial Doppler...
BACKGROUND
Stroke is a devastating complication of sickle cell anemia (SCA) and can be predicted through abnormally high cerebral blood flow velocity using transcranial Doppler Ultrasonography (TCD). The evidence on the role of alpha-thalassemia and glucose-6-phosphate dehydrogenase (G6PD) deficiency in the development of stroke in children with SCA is conflicting. Thus, this study investigated the association of alpha-thalassemia and G6PD(A ) variant with abnormal TCD velocities among Nigerian children with SCA.
METHODS
One hundred and forty-one children with SCA were recruited: 72 children presented with normal TCD (defined as the time-averaged mean of the maximum velocity: < 170 cm/s) and 69 children with abnormal TCD (TAMMV ≥ 200 cm/s). Alpha-thalassemia (the α-3.7 globin gene deletion) was determined by multiplex gap-PCR, while G6PD polymorphisms (202G > A and 376A > G) were genotyped using restriction fragment length polymorphism-polymerase chain reaction.
RESULTS
The frequency of α-thalassemia trait in the children with normal TCD was higher than those with abnormal TCD: 38/72 (52.8%) [α-/ α α: 41.7%, α -/ α -: 11.1%] versus 21/69 (30.4%) [α-/ α α: 27.5%, α -/ α -: 2.9%], and the odds of abnormal TCD were reduced in the presence of the α-thalassemia trait [Odds Ratio: 0.39, 95% confidence interval: 0.20-0.78, p = 0.007]. However, the frequencies of G6PDA variant in children with abnormal and normal TCD were similar (11.6% vs. 15.3%, p = 0.522).
CONCLUSION
Our study reveals the protective role of α-thalassemia against the risk of abnormal TCD in Nigerian children with SCA.
Topics: Adolescent; Anemia, Sickle Cell; Blood Flow Velocity; Case-Control Studies; Cerebrovascular Circulation; Child; Child, Preschool; Female; Follow-Up Studies; Glucosephosphate Dehydrogenase Deficiency; Humans; Male; Nigeria; Prognosis; Stroke; Ultrasonography, Doppler, Transcranial; alpha-Thalassemia
PubMed: 33938598
DOI: 10.1002/jcla.23802 -
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 -
Journal of Diabetes and Metabolic... 2015This study was designed to determine relationship between the glucose metabolism disorder (the insulin resistance and the impaired glucose tolerance) and α-thalassemia.
BACKGROUND
This study was designed to determine relationship between the glucose metabolism disorder (the insulin resistance and the impaired glucose tolerance) and α-thalassemia.
METHODS
In this historical cohort study, 80Alpha-thalassemia carriers and 80 healthy people were enrolled. The participants had no diabetes familial history and the waist circumference and blood pressure were in normal range (waist circumference of less than 102 cm in men, 88 cm in women and blood pressure <120/80 mmHg). The serum insulin level, fasting blood glucose (after 12 hours fasting) and two-hour plasma glucose during an oral glucose tolerance test (2-h OGTT) were measured. Insulin resistance was estimated according to homeostasis model assessment method (HOMA). Chi-square test, independent sample t-test and the relative risk were used for data analysis.
RESULTS
According to FBS and OGTT results, the percentage of diabetes mellitus and pre-diabetes were 1.3% and 33.8% in Alpha-thalassemia carriers, respectively. The control group showed 2.5% diabetic and 13.8% pre-diabetic cases as well. The relative risk for the glucose tolerance impairment (diabetes and pre-diabetes) was 2.78 (95% CI: 1.31-5.88, P = 0.07).Six and a half percent of the Alpha-thalassemia group and 2.5% in the control group had 2.25 ≤ HOMAIR ≤ 3.59 (an intermediate state of Insulin sensitivity) p = 0.443. In the study, there was no subject with insulin resistance (HOMAIR >3.59).
CONCLUSIONS
The possibility of risk enhancement of the impaired glucose tolerance (pre-diabetes and diabetes mellitus) in patients with α-thalassemia is almost three times greater than the normal population without relationship with insulin resistance. Diabetic and pre-diabetic Alpha-thalassemia carrier state is younger than the general population suffering of these disorders.
PubMed: 25722965
DOI: 10.1186/s40200-015-0129-2 -
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 -
Acta Bio-medica : Atenei Parmensis Aug 2022Sickle cell disease (SCD), caused by a mutation in the β-globin gene HBB, is widely distributed in malaria endemic regions. The prevalence of sickle cell trait and... (Review)
Review
Sickle cell disease (SCD), caused by a mutation in the β-globin gene HBB, is widely distributed in malaria endemic regions. The prevalence of sickle cell trait and disease reaches up to 4.8-6% and 0.2% respectively, which is the highest among the Arab Gulf states. Omani population represents a variability of HbS genotype combinations with other Hb genotypes modify the clinical severity of the disease. The most prevalent sickling abnormality in Oman is Hb S/S (SCA) followed by Hb S/β-thalassemia. Omani children with SCD with high Hb F level had less severe disease. More than two-thirds of SCD cases were running a mild course of the disease due to the high prevalence of a-thalassemia trait. The severity index has been correlated with the early age of presentation, the absence of a-thalassemia trait and the lower level of HbF as well as to the existence of different β-globin gene haplotypes. S/ β0 presented with the same clinical severity of S/S while those with S/ β+ had some splenic function into adulthood and were more prone to splenic sequestration. The unique existence of HbS-Oman (a severe variant of sickle hemoglobinopathy) markedly increased the severity of the disease. Compound heterozygotes HbS-Oman resulted in very severe clinical manifestations with transfusion-dependency and hypersplenism early in life. This paper summarizes and reviews βs gene haplotypes in patients with sickle cell anemia (SCA) in Oman. (www.actabiomedica.it).
Topics: Adult; Anemia, Sickle Cell; Child; Haplotypes; Humans; Oman; alpha-Thalassemia; beta-Globins; beta-Thalassemia
PubMed: 36043956
DOI: 10.23750/abm.v93i4.13336