-
BMC Medical Genetics Jan 2020Thalassemia is a group of inherited hemoglobic disorders resulting from defects in the synthesis of one or more of the hemoglobin chains, which is one of the most...
BACKGROUND
Thalassemia is a group of inherited hemoglobic disorders resulting from defects in the synthesis of one or more of the hemoglobin chains, which is one of the most prevalent inherited disorders in southern China. Only few studies reported the molecular characterization of α- and β-Thalassemia in Hubei Province in the central of China.
METHODS
A total of 4889 clinically suspected cases of thalassemia were analyzed by Gap-PCR, PCR-based reverse dot blot (RDB).
RESULTS
1706 (33.8%) subjects harbored thalassemia mutations, including 539 (11.0%) subjects with α-thalassemia, 1140 (23.3%) subjects with β-thalassemia mutations, and 25 (0.51%) subjects with both α- and β-thalassemia mutations. Seven genotypes of α-thalassemia mutations and 29 genotypes of β-thalassemia mutations were characterized. --/αα (66.05%), -α/αα (24.12%), and -α/αα (3.71%) accounted for 93.88% of the α-thalassemia mutations. βIVS-II-654/βN, βCD41-42/βN, βCD17/βN, βCD27-28/βN, βCD71-72/βN, β - 28/βN, β - 29/βN, βCD43/βN, βE/βN, accounting for 96.40% of all β-thalassemia genotypes. Furthermore, mean corpuscular volume (MCV) and mean corpuscular Hb (MCH) were sensitive markers for both β-thalassemia and α-thalassemia with --/αα, but not -α/αα and -α/αα.
CONCLUSIONS
Our data indicated great heterogeneity and extensive spectrum of thalassemias in Hubei province of China.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; China; Female; Genetic Heterogeneity; Genetics, Population; Genotype; Hemoglobins; Humans; Infant; Male; Middle Aged; Mutation; Young Adult; alpha-Thalassemia; beta-Thalassemia
PubMed: 31906886
DOI: 10.1186/s12881-019-0925-5 -
Genome Medicine Feb 2021Noninvasive prenatal testing (NIPT) of recessive monogenic diseases depends heavily on knowing the correct parental haplotypes. However, the currently used family-based...
BACKGROUND
Noninvasive prenatal testing (NIPT) of recessive monogenic diseases depends heavily on knowing the correct parental haplotypes. However, the currently used family-based haplotyping method requires pedigrees, and molecular haplotyping is highly challenging due to its high cost, long turnaround time, and complexity. Here, we proposed a new two-step approach, population-based haplotyping-NIPT (PBH-NIPT), using α-thalassemia and β-thalassemia as prototypes.
METHODS
First, we deduced parental haplotypes with Beagle 4.0 with training on a large retrospective carrier screening dataset (4356 thalassemia carrier screening-positive cases). Second, we inferred fetal haplotypes using a parental haplotype-assisted hidden Markov model (HMM) and the Viterbi algorithm.
RESULTS
With this approach, we enrolled 59 couples at risk of having a fetus with thalassemia and successfully inferred 94.1% (111/118) of fetal alleles. We confirmed these alleles by invasive prenatal diagnosis, with 99.1% (110/111) accuracy (95% CI, 95.1-100%).
CONCLUSIONS
These results demonstrate that PBH-NIPT is a sensitive, fast, and inexpensive strategy for NIPT of thalassemia.
Topics: Genetics, Population; Haplotypes; Humans; Noninvasive Prenatal Testing; Parents; Sample Size; alpha-Thalassemia; beta-Thalassemia
PubMed: 33546747
DOI: 10.1186/s13073-021-00836-8 -
JPMA. the Journal of the Pakistan... Jan 2021To evaluate the frequency of alpha thalassemia and detect mutations in the alpha genes in individuals undergoing premarital screening.
OBJECTIVE
To evaluate the frequency of alpha thalassemia and detect mutations in the alpha genes in individuals undergoing premarital screening.
METHODS
The cross-sectional study was conducted at King Fahad Central Hospital, Jazan, Saudi Arabia, from January 2018 to May 2019, and comprised blood samples of individuals visiting the premarital screening clinic. The samples were analyzed for complete blood counts and haemoglobin electrophoresis. Molecular analysis of samples suspected for alpha thalassemia was done using alpha-globin StripAssay kit. Data was anlaysed using SPSS 20.
RESULTS
Of the 3,970 samples analysed, 1,859(46.83%) were from males and 2,111(53.17%) from females. The overall frequency of suspected alpha thalassemia was 4.43% based upon haematological parameters including complete blood count and haemoglobin electrophoresis. Overall, 80 suspected samples were selected for genetic analyses, and, of them, 76 (95%) were positive for deletional and non-deletional mutations of alpha-globin genes, while 4 (5%) were negative for any of the 21 mutations tested.
CONCLUSIONS
Alpha thalassemia was found to be highly prevalent in the study area.
Topics: Cross-Sectional Studies; Female; Genotype; Humans; Male; Saudi Arabia; alpha-Globins; alpha-Thalassemia
PubMed: 33484530
DOI: 10.47391/JPMA.864 -
Cold Spring Harbor Perspectives in... May 2013α-Thalassemia mutations affect up to 5% of the world's population. The clinical spectrum ranges from an asymptomatic condition to a fatal in utero disease. Hemoglobin H... (Review)
Review
α-Thalassemia mutations affect up to 5% of the world's population. The clinical spectrum ranges from an asymptomatic condition to a fatal in utero disease. Hemoglobin H disease results from mutations of three α-globin genes. Deletional forms result in a relatively mild anemia, whereas nondeletional mutations result in a moderate to severe disease characterized by ineffective erythropoiesis, recurrent transfusions, and growth delay. Hemosiderosis develops secondary to increased iron absorption, as well as transfusion burden. Hemoglobin Bart's hydrops fetalis is usually a fatal in utero disease caused by the absence of α genes. Population screening to identify at-risk couples is essential. Affected pregnancies result in severe fetal and maternal complications. Doppler ultrasonography with intrauterine transfusion therapy may improve the fetal prognosis but creates ethical challenges for the family and health providers.
Topics: Age of Onset; Chronic Disease; Critical Illness; Delayed Diagnosis; Female; Global Health; Heterozygote; Humans; Hydrops Fetalis; Infant, Newborn; Iron Overload; Mutation; Neonatal Screening; Pregnancy; Prenatal Diagnosis; alpha-Thalassemia
PubMed: 23543077
DOI: 10.1101/cshperspect.a011742 -
Cold Spring Harbor Perspectives in... Aug 2012Hemoglobin E (HbE) is an extremely common structural hemoglobin variant that occurs at high frequencies throughout many Asian countries. It is a β-hemoglobin variant,... (Review)
Review
Hemoglobin E (HbE) is an extremely common structural hemoglobin variant that occurs at high frequencies throughout many Asian countries. It is a β-hemoglobin variant, which is produced at a slightly reduced rate and hence has the phenotype of a mild form of β thalassemia. Its interactions with different forms of α thalassemia result in a wide variety of clinical disorders, whereas its coinheritance with β thalassemia, a condition called hemoglobin E β thalassemia, is by far the most common severe form of β thalassemia in Asia and, globally, comprises approximately 50% of the clinically severe β-thalassemia disorders.
Topics: 5'-Nucleotidase; Adaptation, Physiological; Alternative Splicing; Genome-Wide Association Study; Genotype; Hemoglobin E; Heterozygote; Homozygote; Humans; Mutation; Phenotype; RNA, Messenger; alpha-Thalassemia; beta-Thalassemia
PubMed: 22908199
DOI: 10.1101/cshperspect.a011734 -
Cellular and Molecular Life Sciences :... Apr 2009Recent work in the alpha thalassaemia field has started to provide some indication of the mechanisms involved in the very high frequency of the different forms of alpha... (Review)
Review
Recent work in the alpha thalassaemia field has started to provide some indication of the mechanisms involved in the very high frequency of the different forms of alpha thalassaemia among the populations of tropical countries, and, at the same time, is starting to define at least some of the mechanisms for its remarkable phenotypic heterogeneity. These diseases continue to provide extremely valuable models for the better understanding of the regulation of the alpha globin genes, and for human molecular pathology in general. The much less common disorders, ATR-16 and ATR-X are also providing valuable information about the spectrum of molecular lesions associated with different forms of mental retardation and about the molecular mechanisms involved in their varying phenotypes.
Topics: Genetic Variation; Genetics, Population; Genotype; Hemoglobins; Humans; Mental Retardation, X-Linked; Neural Tube Defects; Phenotype; Tropical Medicine; alpha-Globins; alpha-Thalassemia
PubMed: 19020805
DOI: 10.1007/s00018-008-8529-9 -
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 -
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 -
The Indian Journal of Medical Research Oct 2011In Southeast Asia α-thalassaemia, β-thalassaemia, haemoglobin (Hb) E and Hb Constant Spring (CS) are prevalent. The abnormal genes in different combinations lead to... (Review)
Review
In Southeast Asia α-thalassaemia, β-thalassaemia, haemoglobin (Hb) E and Hb Constant Spring (CS) are prevalent. The abnormal genes in different combinations lead to over 60 different thalassaemia syndromes, making Southeast Asia the locality with the most complex thalassaemia genotypes. The four major thalassaemic diseases are Hb Bart's hydrops fetalis (homozygous α-thalassaemia 1), homozygous β-thalassaemia, β-thalassaemia/Hb E and Hb H diseases. α-Thalassaemia, most often, occurs from gene deletions whereas point mutations and small deletions or insertions in the β-globin gene sequence are the major molecular defects responsible for most β-thalassaemias. Clinical manifestations of α-thalassaemia range from asymptomatic cases with normal findings to the totally lethal Hb Bart's hydrops fetalis syndrome. Homozygosity of β-thalassaemia results in a severe thalassaemic disease while the patients with compound heterozygosity, β-thalassaemia/Hb E, present variable severity of anaemia, and some can be as severe as homozygous β-thalassaemia. Concomitant inheritance of α-thalassaemia and increased production of Hb F are responsible for mild clinical phenotypes in some patients. However, there are still some unknown factors that can modulate disease severity in both α- and β-thalassaemias. Therefore, it is possible to set a strategy for prevention and control of thalassaemia, which includes population screening for heterozygotes, genetic counselling and foetal diagnosis with selective abortion of affected pregnancies.
Topics: Asia, Southeastern; Gene Deletion; Hemoglobin E; Hemoglobins, Abnormal; Humans; Point Mutation; alpha-Thalassemia; beta-Globins; beta-Thalassemia
PubMed: 22089614
DOI: No ID Found -
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