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Frontiers in Genetics 2022There are limited studies on the molecular profile of thalassemia in Hainan, the free trade island in China. Our aim was to reveal the prevalence and molecular mutation...
There are limited studies on the molecular profile of thalassemia in Hainan, the free trade island in China. Our aim was to reveal the prevalence and molecular mutation spectrum of thalassemia in different ethnic groups and regions of Hainan through a large sample study for the first time. A total of 231,596 individuals from 19 cities and counties in Hainan were screened by hematological parameter analysis, and further genetic analysis was performed on individuals with MCV less than 82 fL. Totally, 31,780 (13.72%) subjects were diagnosed as thalassemia carriers. The overall prevalence of α-thalassemia, β-thalassemia, and α+β-thalassemia were 11.04%, 1.48%, and 1.20%, respectively. We further analyzed the molecular profiles of thalassemia in various ethnic groups and mainly compared the difference between Han and Li. The results showed that the frequency of thalassemia in the Li population (47.03%) was much higher than that in Han (9.37%). Except for β-thalassemia (1.31% of Li vs. 1.47% of Han), the frequencies of α-thalassemia (39.59% of Li vs. 7.35% of Han) and α+β-thalassemia (6.13% of Li vs. 0.56% of Han) in the Li were obviously higher than those in Han. The high-frequent genotypes of α-thalassemia in Han were αα/-- (25.55%), -α/αα (22.17%), -α/αα (21.59%), αα/αα (8.93%), and -α/-α (4.17%) and those of Li were -α/αα (17.24%), -α/αα (17.16%), -α/-α (15.09%), αα/αα (9.69%), and αα/-α (8.06%), respectively. The αα/-- was the highest genotype of α-thalassemia in Han but only accounted for 1.87% in Li. For β-thalassemia, the top three high-frequent genotypes in both Han and Li were β/β, β/β, and β/β, but the frequency of β/β in Li (90.96%) was much higher than that in Han (56.32%) and the data reported in other provinces of China. Additionally, the prevalence of thalassemia ranged from 8.16% to 34.35% in Hainan, Wuzhishan, Baoting, Qiongzhong, and Baisha have a higher prevalence than other areas. Our study revealed the characteristics of ethnic and regional differences in the prevalence of thalassemia in the childbearing age population of Hainan for the first time, indicating that the prevalence of thalassemia among Li nationality is the highest in China. Those findings will be useful for genetic counseling and the prevention of thalassemia.
PubMed: 35783269
DOI: 10.3389/fgene.2022.874624 -
Orphanet Journal of Rare Diseases Jul 2023Inherited blood disorders affect 7% of the population worldwide, with higher prevalences in countries in the "thalassemia belt," which includes Bangladesh. Clinical... (Clinical Trial)
Clinical Trial
BACKGROUND
Inherited blood disorders affect 7% of the population worldwide, with higher prevalences in countries in the "thalassemia belt," which includes Bangladesh. Clinical management options for severely affected individuals are expensive; thus, targeted government policies are needed to support prevention and treatment programs. In Bangladesh, there is a lack of data, in particular community-based estimates, to determine population prevalence. This study aims to estimate the prevalence of a wide range of hemoglobinopathies and their associations with anemia in a community-based sample of women and young children in rural Sylhet, Bangladesh.
METHODS
Capillary blood samples from 900 reproductive-aged women and 395 children (aged 6-37 months) participating in the Food and Agricultural Approaches to Reducing Malnutrition (FAARM) trial in two sub-districts of Habiganj, Sylhet Division, Bangladesh were analyzed for alpha thalassemia, beta thalassemia, and other hemoglobinopathies. We examined the association of each inherited blood disorder with hemoglobin concentration and anemia using linear and logistic regression.
RESULTS
We identified at least one inherited blood disorder in 11% of women and 10% of children. Alpha thalassemia was most prevalent, identified in 7% of women and 5% of children, followed by beta thalassemia and hemoglobin E in 2-3%. We also identified cases of hemoglobin S and hemoglobin D in this population. Having any of the identified inherited blood disorders was associated with lower hemoglobin values among non-pregnant women, largely driven by alpha and beta thalassemia. Pregnant women with beta thalassemia were also more likely to have lower hemoglobin concentrations. Among children, we found weak evidence for a relationship between hemoglobinopathy and lower hemoglobin concentrations.
CONCLUSIONS
We found a high prevalence of alpha thalassemia among both women and children in rural Sylhet, Bangladesh-higher than all other identified hemoglobinopathies combined. Community-based estimates of alpha thalassemia prevalence in Bangladesh are scarce, yet our findings suggest that alpha thalassemia may comprise the majority of inherited blood disorders in some regions of the country. We recommend that future research on inherited blood disorders in Bangladesh include estimates of alpha thalassemia in their reporting for public health awareness and to facilitate couples counseling.
Topics: Adult; Child, Preschool; Female; Humans; Infant; alpha-Thalassemia; Bangladesh; beta-Thalassemia; Hemoglobinopathies; Prevalence
PubMed: 37468973
DOI: 10.1186/s13023-023-02821-3 -
PloS One 2021Thalassemia is a severe disease that occurs due to abnormalities in hemoglobin genes. Various genetic factors in different populations lead to different clinical...
BACKGROUND
Thalassemia is a severe disease that occurs due to abnormalities in hemoglobin genes. Various genetic factors in different populations lead to different clinical manifestations of thalassemia disease, particularly among people who have a long history of migration and who have married among tribes, such as the hill tribe people in Thailand. This genetic epidemiological study aimed to estimate the prevalence of various forms of thalassemia among the six main hill tribe populations in Thailand.
METHODS
A cross-sectional study was conducted to obtain information and blood specimens from school children belonging to one of the six main hill tribes in Thailand: Akha, Lau, Hmong, Yao, Karen, and Lisu. Hill tribe children who were attending grades 4-6 in 13 selected schools in Chiang Rai Province, Thailand, were invited to participate in the study. A validated questionnaire and 3 mL blood specimens were collected after obtaining information consent forms from both the children and their parents on a voluntary basis. A complete blood count (CBC) was performed, followed by osmotic fragility (OF) and dichlorophenol indophenol precipitation (DCIP) tests to screen for thalassemia. High-performance liquid chromatography (HPLC) and real-time quantitative polymerase chain reaction (qPCR) were used to identify hemoglobin type and α-thalassemia, respectively. A t-test, chi-square and logistic regression were used to detect the associations between variables at the significance level of α = 0.05.
RESULTS
A total of 1,200 participants from 6 different tribes were recruited for the study; 50.0% were males, and 67.3% were aged 11-12 years. The overall prevalence of thalassemia carriers according to the screening tests was 9.8% (117 of 1,200). Among the cases, 83 were A2A (59 cases were α-thalassemia 1 carrier or α-thalassemia 2 carrier or homozygous α-thalassemia 2, and 24 cases were β-thalassemia trait with or without α-thalassemia); 1 case was EE (homozygous Hb E with or without α-thalassemia); 31 cases were EA (30 cases were the Hb E trait, and 1 case was Hb E trait with or without α-thalassemia); 1 case was A2A Bart's H (Hb H disease α-thalassemia 1/α-thalassemia 2); and 1 case was A2A with abnormal Hb. The prevalence of the α-thalassemia 1 trait among the hill tribe population was 2.5%. The greatest prevalence of the α-thalassemia 1 trait was found in the Karen (3.0%) and Hmong (3.0%) tribes.
CONCLUSIONS
The prevalence of some forms of thalassemia in the hill tribe population is higher than that in the Thai and other populations. Effective and available thalassemia screening tests, including essential information to protect the next generation through the specific counseling clinic, are crucial, particularly due to increasing marriages within these populations.
Topics: Blood Cell Count; Child; Cross-Sectional Studies; Female; Humans; Indigenous Peoples; Male; Population Groups; Prevalence; Thailand; Thalassemia
PubMed: 33571309
DOI: 10.1371/journal.pone.0246736 -
Genes Aug 2022Congenital malformations diagnosed by ultrasound screening complicate 3-5% of pregnancies and many of these have an underlying genetic cause. Approximately 40% of... (Review)
Review
Congenital malformations diagnosed by ultrasound screening complicate 3-5% of pregnancies and many of these have an underlying genetic cause. Approximately 40% of prenatally diagnosed fetal malformations are associated with aneuploidy or copy number variants, detected by conventional karyotyping, QF-PCR and microarray techniques, however monogenic disorders are not diagnosed by these tests. Next generation sequencing as a secondary prenatal genetic test offers additional diagnostic yield for congenital abnormalities deemed to be potentially associated with an underlying genetic aetiology, as demonstrated by two large cohorts: the 'Prenatal assessment of genomes and exomes' (PAGE) study and 'Whole-exome sequencing in the evaluation of fetal structural anomalies: a prospective cohort study' performed at Columbia University in the US. These were large and prospective studies but relatively 'unselected' congenital malformations, with little Clinical Genetics input to the pre-test selection process. This review focuses on the incremental yield of next generation sequencing in single system congenital malformations, using evidence from the PAGE, Columbia and subsequent cohorts, with particularly high yields in those fetuses with cardiac and neurological anomalies, large nuchal translucency and non-immune fetal hydrops (of unknown aetiology). The total additional yield gained by exome sequencing in congenital heart disease was 12.7%, for neurological malformations 13.8%, 13.1% in increased nuchal translucency and 29% in non-immune fetal hydrops. This demonstrates significant incremental yield with exome sequencing in single-system anomalies and supports next generation sequencing as a secondary genetic test in routine clinical care of fetuses with congenital abnormalities.
Topics: Female; Fetus; High-Throughput Nucleotide Sequencing; Humans; Hydrops Fetalis; Infant, Newborn; Pregnancy; Pregnancy Trimester, First; Prospective Studies; Ultrasonography, Prenatal
PubMed: 36140685
DOI: 10.3390/genes13091517 -
Expert Opinion on Therapeutic Targets Jul 2018ATRX is a chromatin remodeling protein whose main function is the deposition of the histone variant H3.3. ATRX mutations are widely distributed in glioma, and correlate... (Review)
Review
ATRX is a chromatin remodeling protein whose main function is the deposition of the histone variant H3.3. ATRX mutations are widely distributed in glioma, and correlate with alternative lengthening of telomeres (ALT) development, but they also affect other cellular functions related to epigenetic regulation. Areas covered: We discuss the main molecular characteristics of ATRX, from its various functions in normal development to the effects of its loss in ATRX syndrome patients and animal models. We focus on the salient consequences of ATRX mutations in cancer, from a clinical to a molecular point of view, focusing on both adult and pediatric glioma. Finally, we will discuss the therapeutic opportunities future research perspectives. Expert opinion: ATRX is a major component of various essential cellular pathways, exceeding its functions as a histone chaperone (e.g. DNA replication and repair, chromatin higher-order structure regulation, gene transcriptional regulation, etc.). However, it is unclear how the loss of these functions in ATRX-null cancer cells affects cancer development and progression. We anticipate new treatments and clinical approaches will emerge for glioma and other cancer types as mechanistic and molecular studies on ATRX are only just beginning to reveal the many critical functions of this protein in cancer.
Topics: Adult; Animals; Child; Chromatin Assembly and Disassembly; Epigenesis, Genetic; Glioma; Humans; Mental Retardation, X-Linked; Mutation; Telomere Homeostasis; X-linked Nuclear Protein; alpha-Thalassemia
PubMed: 29889582
DOI: 10.1080/14728222.2018.1487953 -
Haematologica Mar 2020
Topics: Anemia, Hemolytic, Congenital; Cell Differentiation; Erythroblasts; Humans; Hydrops Fetalis; Ion Channels; Stem Cells
PubMed: 32115411
DOI: 10.3324/haematol.2019.233999 -
International Journal of General... 2021Carrier screening is the most effective means of controlling the prevalence of alpha-thalassemia. However, due to the differences in ethnic populations and genotypes,...
BACKGROUND
Carrier screening is the most effective means of controlling the prevalence of alpha-thalassemia. However, due to the differences in ethnic populations and genotypes, the distribution of mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and hemoglobin A (HbA) varies in different regions. This study aimed to examine screening efficiency of these indicators in different genotypes of alpha-thalassemia in Fujian Province, China.
METHODS
The data of 13,294 subjects collected from May 2016 to December 2019 were reviewed. The participants were categorized as alpha-thalassemia group and negative-for-alpha-thalassemia group based on the results of the genetic analysis. The distribution of MCV, MCH, and HbA in different groups was analysed statistically. And the screening efficiency of different indicators and schemes was compared in different genotypes. The positive criteria of MCV < 80fL, MCH < 27pg, and Hb A< 2.5% were applied.
RESULTS
Among the 13,294 subjects, 2658 were alpha-thalassemia carriers. The genotypes of -/αα and -α/αα are the most prevalent with 63.9% and 21.9% in Fujian Province, China. There were significant differences in the distribution of the three indicators in different groups. The detection rate of the three indicators combined screening was 92.6%.
CONCLUSION
The distribution of the three indicators overlapped partly between alpha-thalassemia group and negative-for-alpha-thalassemia group. They showed significant differences in the median comparison of seven common genotypes. Combined screening with MCV, MCH and HbA improved the detection rate of alpha-thalassemia. The results of this study provide a data basis for clinical laboratories and a reliable reference for clinical consultation.
PubMed: 34737627
DOI: 10.2147/IJGM.S338419 -
BMC Medicine Oct 2023Single low-dose primaquine (SLDPQ) effectively blocks the transmission of Plasmodium falciparum malaria, but anxiety remains regarding its haemolytic potential in... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Single low-dose primaquine (SLDPQ) effectively blocks the transmission of Plasmodium falciparum malaria, but anxiety remains regarding its haemolytic potential in patients with glucose-6-phopshate dehydrogenase (G6PD) deficiency. We, therefore, examined the independent effects of several factors on haemoglobin (Hb) dynamics in falciparum-infected children with a particular interest in SLDPQ and G6PD status.
METHODS
This randomised, double-blind, placebo-controlled, safety trial was conducted in Congolese and Ugandan children aged 6 months-11 years with acute uncomplicated P. falciparum and day (D) 0 Hbs ≥ 6 g/dL who were treated with age-dosed SLDPQ/placebo and weight-dosed artemether lumefantrine (AL) or dihydroartemisinin piperaquine (DHAPP). Genotyping defined G6PD (G6PD c.202T allele), haemoglobin S (HbS), and α-thalassaemia status. Multivariable linear and logistic regression assessed factor independence for continuous Hb parameters and Hb recovery (D42 Hb > D0 Hb), respectively.
RESULTS
One thousand one hundred thirty-seven children, whose median age was 5 years, were randomised to receive: AL + SLDPQ (n = 286), AL + placebo (286), DHAPP + SLDPQ (283), and DHAPP + placebo (282). By G6PD status, 284 were G6PD deficient (239 hemizygous males, 45 homozygous females), 119 were heterozygous females, 418 and 299 were normal males and females, respectively, and 17 were of unknown status. The mean D0 Hb was 10.6 (SD 1.6) g/dL and was lower in younger children with longer illnesses, lower mid-upper arm circumferences, splenomegaly, and α-thalassaemia trait, who were either G6PDd or heterozygous females. The initial fractional fall in Hb was greater in younger children with higher D0 Hbs and D0 parasitaemias and longer illnesses but less in sickle cell trait. Older G6PDd children with lower starting Hbs and greater factional falls were more likely to achieve Hb recovery, whilst lower D42 Hb concentrations were associated with younger G6PD normal children with lower fractional falls, sickle cell disease, α-thalassaemia silent carrier and trait, and late treatment failures. Ten blood transfusions were given in the first week (5 SLDPQ, 5 placebo).
CONCLUSIONS
In these falciparum-infected African children, posttreatment Hb changes were unaffected by SLDPQ, and G6PDd patients had favourable posttreatment Hb changes and a higher probability of Hb recovery. These reassuring findings support SLDPQ deployment without G6PD screening in Africa.
TRIAL REGISTRATION
The trial is registered at ISRCTN 11594437.
Topics: Male; Female; Humans; Child; Child, Preschool; Primaquine; Antimalarials; alpha-Thalassemia; Artemether, Lumefantrine Drug Combination; Artemether; Malaria, Falciparum; Hemoglobins; Glucosephosphate Dehydrogenase Deficiency; Plasmodium falciparum
PubMed: 37858129
DOI: 10.1186/s12916-023-03105-0 -
Scientific Reports Jun 2023α-Thalassaemia is an inherited haemoglobin disorder that results from the defective synthesis of α-globin protein. Couples whom both carry the α-thalassaemia 1 gene...
α-Thalassaemia is an inherited haemoglobin disorder that results from the defective synthesis of α-globin protein. Couples whom both carry the α-thalassaemia 1 gene are at risk of having a foetus with the most severe thalassaemia, Hb Bart's hydrops fetalis, with a risk of maternal mortality. However, haematological parameters alone cannot distinguish between a α-thalassaemia 1 carrier and a homozygous α-thalassaemia 2, in which one α-globin gene has been deleted on each chromosome. A rapid and accurate molecular detection assay is essential for prevention of the disease in populations where α-thalassaemia 1 is common. Multiplex Gap-PCR analysis is widely used for diagnosis of α-thalassaemia. However, the technique requires a thermocycler and post-amplification processing, which limits its application in primary care or in rural areas in developing countries. Loop mediated isothermal amplification (LAMP) amplifies target DNA at a constant temperature and does not require a thermocycler. This study developed a colorimetric Gap-LAMP using malachite green to allow naked eye visualization of two deletional α-thalassaemia 1 commonly found in Asian populations, the Southeast Asian type (--) and the Thai type (--) deletions. The Gap-LAMP was performed on DNA samples from 410 individuals carrying various α-thalassaemia gene defects with 100% concordance with conventional Gap-PCR analysis. This method eliminates post-amplification processing or the use of expensive sophisticated equipment and allows screening large populations for the prevention and control of α-thalassaemia.
Topics: Humans; Female; alpha-Thalassemia; Colorimetry; Hemoglobinopathies; Hydrops Fetalis
PubMed: 37311778
DOI: 10.1038/s41598-023-36676-2 -
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