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PubMed1996

Increased procoagulant activity of red blood cells from patients with homozygous sickle cell disease and beta-thalassemia.

It has recently been proved that, in vitro, red blood cells (RBCs) from patients with homozygous beta-thalassemia behave as procoagulant cells. The procoagulant activity of beta-thalassemia RBCs might be the result of an increased exposure of procoagulant phospholipids (i.e. phosphatidylserine) in the outer leaflet of the membrane. In order to test this hypothesis, we compared the catalytic properties of RBCs of patients with beta-thalassemia and homozygous sickle cell disease (SS-RBCs) with that of controls. The catalytic parameters (Km, kcat) of prothrombin activation by factor Xa were determined both in the absence and in the presence of RBCs. The turn-over number (kcat) of the reaction was not modified by normal, SS- or beta-thalassemia RBCs. The Km was lower in the presence of normal RBCs (mean value: 9.1 microM) than in the absence of cells (26 microM). The Km measured in the presence of either SS-RBCs (mean value: 1.6 microM) or beta-thalassemia RBCs (mean value: 1.5 microM) was significantly lower compared to normal RBCs (p < 0.001). No significant difference was observed between SS-RBCs and beta-thalassemia RBCs. Annexin V, a protein with high affinity and specificity for anionic phospholipids, inhibited the procoagulant activity of both SS-RBCs and beta-thalassemia RBCs, in a dose-dependent manner. More than 95% inhibition was achieved at nanomolar concentrations of annexin V. These results indicate that the procoagulant activity of both beta-thalassemia RBCs and SS-RBCs may be fully ascribed to an abnormal exposure of phosphatidylserine at the outer surface of the red cells.

Adolescent↗

PubMed1998

[Beta-thalassemia and Hb D in patients with anemia].

Twelve patients with anemias and their close relatives were examined: 8 adults (3 men and 5 women) and 4 children (3 boys and 1 girl). Six of them were Armenians, 1 woman was Russian, and the rest were of mixed origin: 3 Russian-Azerbaijan-Ukrainian, 1 child Russian-Ukrainian-African, and 1 woman Russian-Ukrainian. Hemoglobinopathies were detected in 10 subjects from 4 families (3 families from Donetsk and 1 from Moscow). Homozygotic beta-thalassemia major (Hb F 98.9%) was diagnosed in a 2-year-old Armenian girl from Donetsk. The girl lags behind in development and suffers from anemia with hepatosplenomegaly and jaundice. Heterozygotic beta-thalassemia minor with increased levels of Hb A2 and Hb F was diagnosed in her parents (Armenians from Azerbaijan). A 15-year-old Russian-Azerbaijan-Ukrainian boy from another family in Donetsk had beta-thalassemia with HbD (94%). The boy suffers from anemia with hepatosplenomegaly, jaundice, and chronic hepatitis. Heterozygotic beta-thalassemia with increased levels of Hb A2 and Hb F was revealed in proband's mother and brother; the father was not examined. alpha-Thalassemia is suspected in a 3-year-old boy from a Russian-Ukrainian-African family in Donetsk; he presented with a very small "fast" abnormal hemoglobin fraction. The boy suffers from anemia with splenomegaly and systolic murmur. Blurred form of thalassemia minor is diagnosed in the mother. The father, an African from Zaire, was not examined. Heterozygotic beta-thalassemia with increased Hb A2 level was revealed in a 20-year-old Armenian boy from Moscow. He presented with manifest splenomegaly, chronic gastritis, and mitral valve prolapse. His mother suffers from thalassemia minor, was anemic during pregnancy, and there are cases of anemia in the family. No hematologic disorders were found in the father. No hemoglobinopathies were detected in a 59-year-old Russian women from the town of Tver with very grave anemia; apparently, her condition was acquired, but not hereditary. Data on patients in the city of Donetsk are of special interest, for there are virtually no reports about hemoglobinopathies in the Ukraine.

Adolescent↗

PubMed1997

Molecular and hematological characterization of HbE heterozygote with alpha-thalassemia determinant.

Hemoglobin E and alpha-thalassemia are prevalent in Thailand. The chance that an individual heterozygous for HbE also carries an alpha-thalassemia determinant is high. In this individual, the amount of HbE and other hematological parameters may be differed from that of usual observation. In this study, a total of 132 HbE heterozygotes were screened for alpha-thalassemia 1 gene deletion by the polymerase chain reaction. Out of 132 cases, 71 could be completely analyzed for hematologic parameters. Forty-three of 88 cases with HbE less than 25% as measured using microcolumn chromatography were positive for this gene deletion. In twenty of these 43 alpha-thalassemia 1 positive cases, the average values of Hb, Hct, MCV, MCH, MCHC, RDW and HbE were 10.6 g/ dl, 33.1%, 64.8 fl, 21.0 pg, 32.3 pg/dl, 18.6% and 17.4%, respectively. Eight of 9 alpha-thalassemia 1 negative cases were positive for alpha-thalassemia 2 gene deletion in Southern blot analysis. In this later group, hematological parameters were similar to that of the former. Co-inheritance of the Hb Constant Spring gene has no direct effect on the level of HbE. No alpha-thalassemia 1 gene was detected in the remaining 34 cases whose HbE were above 25%. The average amount of Hb, Hct, MCV, MCH, MCHC, RDW and HbE were 12.4 g/dl, 37.7%, 79.7 fl, 26.2 pg, 32.7 pg/dl, 25.8% and 28.5%, respectively. Therefore, screening for HbE level below 25% may be a convenient way of identifying parents of carrying alpha-thalassemia 1 determinant.

Erythrocytes↗

PubMed2004

Flow cytometric quantitation of red blood cell vesicles in thalassemia.

BACKGROUND: Thalassemia is a hereditary hemolytic anemia caused by mutations in the globin gene complex. Circulatory disturbances including arterial and venous thrombosis have also been noted in these patients. Aggregability of abnormal RBC and the high level of membrane-derived microparticles stemming from activated platelets and other blood cells are thought to be responsible for the associated thrombotic risk. Destruction of RBC is also thought to be an important pathophysiological consequence, particularly through the formation of circulating vesicles. To our knowledge, there has been no attempt to quantitatively evaluate the number of RBC vesicles in thalassemia. This prompted us to study the level of RBC vesicles in the peripheral blood of thalassemia patients using quantitative flow cytometry. METHODS: Whole blood from each subject was doubly stained for RBC and platelet or annexin V markers, together with the known density TruCount beads. RBC vesicles were gated according to their forward/side scatter and RBC marker. Percentage of RBC vesicles and their absolute number were analyzed by flow cytometry. RESULTS: Our data indicated that RBC vesicles were annexin V-positive. The number of annexin V-positive events was higher than their intact RBCs. RBC vesicles were present in both normal and thalassemic blood samples, but the numbers of RBC vesicles were significantly higher in thalassemia. Both the percentage and the absolute number of RBC vesicles were especially marked in splenectomized subjects with beta-thalassemia/Hemoglobin E. When clinical and hematological indices were compared with RBC vesicles, there was an inverse relationship between the degree of severity in thalassemia patients and the number of RBC vesicles. CONCLUSION: Flow cytometric quantitation of RBC vesicles is simple, reliable and may offer new insights in to study of the relationship between defective hemoglobin synthesis, RBC perturbation and pathophysiological complications in thalassemia.

Adolescent↗

PubMed2006

Successful preimplantation genetic diagnosis for alpha- and beta-thalassemia in China.

METHODS & RESULTS: In southern China, the average carrier rates of alpha-thalassemia and beta-thalassemia in the population are as high as 10.3% and 2.8%, respectively. Because of the high rates, they are known as 'social diseases' in some regions. In this study, the fluorescent gap PCR, which can detect the alpha-thalassemia Southeast Asia deletion (SEA deletion), was applied in four clinical applications of preimplantation genetic diagnosis (PGD) on four couples, among whom both partners were alpha-thalassemia carriers. Two patients became pregnant and two healthy babies were born, which confirmed the PGD results. The single cell multiplex nested PCR followed by reverse dot blot (RDB), which can simultaneously detect the 16 beta-thalassemia mutations in the Chinese population, was applied in four clinical PGD cycles on four couples among whom both partners were beta-thalassemia carriers. One pregnancy was achieved and it resulted in a live healthy birth, which confirmed the results of PGD. The amplification efficiencies of the two protocols described above were 89.5% and 93.9%, respectively. The allele drop-out (ADO) rates of these two protocols were 5.9% and 10.9%, respectively. CONCLUSION: These studies represent the successful applications of PGD protocols that can detect more than 95% of alpha- and beta -thalassemia mutations in the Chinese population.

Adult↗

PubMed2025

Identification of maternal Gγ(Aγδβ)0 thalassemia through retrospective reanalysis of prenatal cfDNA sequencing data.

OBJECTIVE: Non-invasive prenatal screening (NIPS) is widely used to detect chromosomal abnormalities such as trisomies 21, 13, and 18 and is also effective in screening for copy number variations (CNVs). However, the routine application of NIPS to detect smaller CNVs within the HBB gene, specifically Gγ(Aγδβ)0 thalassemia, has yet to be well documented. This study aims to evaluate the efficacy of cfDNA-based maternal carrier screening in routine screening for Gγ(Aγδβ)0 thalassemia. METHODS: We performed a retrospective analysis of 107,300 pregnant women who underwent NIPS at Longgang Maternal and Child Healthcare Hospital in Shenzhen from December 2017 to May 2022. Using an improved algorithm, we reanalyzed NIPS data to identify maternal Gγ(Aγδβ)0 thalassemia. Positive cases were confirmed by multiplex ligation-dependent probe amplification (MLPA) using peripheral blood leukocytes. RESULTS: Among the 107,300 NIPS analyses, 38 maternal deletion CNVs within the HBB gene were identified using the improved algorithm, with a prevalence of 0.035% (38/107,300). MLPA confirmed that all detected deletions were consistent with Gγ(Aγδβ)0 thalassemia. The positive predictive value (PPV) for detecting Gγ(Aγδβ)0 thalassemia by cfDNA-based maternal carrier screening was 100%. Among the 38 Gγ(Aγδβ)0 cases, 9 were also associated with α-thalassemia deletions, including 4 cases with -SEA/αα, 4 with -α3.7/αα, and 1 with -α4.2/αα. No cases of homozygosity or compound HBB gene variants were observed. CONCLUSIONS: Gγ(Aγδβ)0 thalassemia is not uncommon in China, and repurposed NIPS methodology for maternal genomic analysis in detecting HBB gene deletions is a reliable method for identifying maternal carriers of this disease.

Humans↗

PubMed1994

Thalassemia: pathophysiology of red cell changes.

The thalassemias are extremely heterogeneous in terms of their clinical severity, and their underlying pathophysiology relates directly to the extent of accumulation of excess unmatched globin chains: alpha in beta thalassemia and beta in the alpha thalassemias. However, the accumulation of each separate globin chain affects red cell membrane material properties and the state of red cell hydration very differently. These observations presumably account for the varying extent of ineffective erythropoiesis and peripheral blood hemolysis in the major variants of thalassemia. The thalassemias are a worldwide group of inherited disorders of globin-chain synthesis that developed in multiple geographic regions, probably because they provided partial protection against malaria. In normal assembly of adult hemoglobin (HbA-alpha 2 beta 2), alpha and beta globin are synthesized by genes on different chromosomes, whereas heme is synthesized primarily on mitochondria. The synthesis of these chains is very tightly coordinated so that the ratio of alpha globin to beta globin (beta in this case including the beta-like globins delta and gamma) is normally 1 +/- 0.05. Furthermore, specific erythroid proteases are designed to attack and destroy excess alpha or beta globin chains, demonstrating the deleterious impact of the accumulation of excess unmatched globin chains. In beta thalassemia, production of beta globin decreases and excess alpha globin accumulates. In alpha thalassemia, on the other hand, this process occurs in reverse. Perhaps in these disorders more than any others, molecular biologists have documented the deletional and transcriptional events leading to diminished synthesis of specific classes of globin chains.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2000

Thalassemia syndromes in Saudi Arabia. Meta-analysis of local studies.

The geographical distribution of Alpha and Beta-Thalassemias differ markedly. Alpha-Thalassemia being particularly prevalent in Southeast Asia and Beta-Thalassemia in the Mediterranean basin. Thalassemia syndromes are common in Saudi Arabia: the Beta-Thalassemia genes occur with variable frequency in different regions of Saudi Arabia and both B+ and Bo thalassemia have been reported. Alpha-Thalassemia is also highly prevalent here and the interaction with the sickle cell gene is commonly observed. Over the last few years, a great deal of information regarding the clinical, molecular and management of these disorders has accumulated in the literature. In this paper we summarize some of the recent studies on the subject along with our experience and our attempt to highlight a number of questions still awaiting answers.

Gene Deletion↗

PubMed2002

Polymorphism analysis in the COLIA1 gene of patients with thalassemia major and intermedia.

beta-Thalassemia, an inherited blood disorder, mainly affects people from the Mediterranean region. This life-threatening anemia is so severe that regular blood transfusions and iron-chelating therapy is obligatory throughout life. Commonly occurring complications, especially in adult patients, are osteopenia and osteoporosis. Osteoporotic fractures are strongly associated with bone density, which is under polygenic control. Type I collagen, which is encoded by the COLIA1 and COLIA2 genes, is the major protein in the bone. A G-->T polymorphism in the regulatory region of the COLIA1 gene at a recognition site for transcription factor Sp1 has been strongly associated with osteoporotic fractures. In this study, the G-->T polymorphism is screened in 42 beta-thalassemia major and 10 beta-thalassemia intermedia patients. 64.3% of the beta-thalassemia patients were heterozygotes for G/T (Ss) polymorphism and 35.7% were homozygous for G/G (SS), 60% of the beta-thalassemia intermedia patients were heterozygous (Ss) and 40% were homozygous (ss). The number of heterozygotes in the beta-thalassemia major group was significantly higher, compared to the control group (F = 13.615, P = 0.001). The number of heterozygotes in beta-thalassemia intermedia group was also significantly higher, compared to the control group (F = 5.158, P = 0.029). Patients who are G/T heterozygotes (Ss) at the polymorphic Sp1 site have a lower bone mineral density than G/G homozygotes (SS) (P = 0.01).

Adult↗

PubMed2002

Plasma chitotriosidase activity in patients with beta-thalassemia.

Variable increases in chitotriosidase levels have been reported in Italian patients with beta-thalassemia major and intermedia. We measured plasma chitotriosidase levels in Israeli patients with beta-thalassemia to ascertain its use as a universal marker of disease and/or response to therapy. Chitotriosidase levels in 39 adults (16-53 years; 30 with beta-thalassemia major, 9 with intermedia), and in 14 children (0.7-15 years; 12 with beta-thalassemia major, 2 with intermedia) were compared with other measures of disease, such as ferritin, hemoglobin, liver function tests, and genotype. Plasma chitotriosidase levels were normal (0.37 +/- 0.04 mU/mL) in all children. Twelve adults (31%) had elevated levels (>1.33 mU/mL): 11 patients (37%) with thalassemia major and 1 patient (11%) with thalassemia intermedia. A significant correlation was only found between plasma chitotriosidase levels and ferritin levels, and with mean number of transfusions per year. The patient with the highest chitotriosidase (1,440 nmol/mL/hr) had the highest ferritin (5,175 microg/L), required the most transfusions per year (40), and had abnormal liver tests. Normal chitotriosidase levels in the pediatric cohort and increased levels in only some adults may reflect status of iron overload in macrophages; thus there may be a role for monitoring chitotriosidase in patients with beta-thalassemia. Our results confirm results of the Italian cohort; however, in the latter, a more universal correlation was noted and chitotriosidase levels were much higher.

Adolescent↗

PubMed2005

Molecular genetic confirmatory testing from newborn screening samples for the common African-American, Asian Indian, Southeast Asian, and Chinese beta-thalassemia mutations.

beta-Thalassemia is a serious health problem in the United States, especially in California, due to increased Asian immigration. Neonatal screening by using high-performance liquid chromatography (HPLC) or isoelectric focusing (IEF) may lead to confusion due to interactions of various hemoglobinopathies with beta-thalassemia. Our purpose was to develop single-tube multiplexed PCR assays using original neonatal screening specimens to identify the mutations responsible for beta-thalassemia in order to expedite diagnostic confirmation. Primers were designed for two to six common ethnic-specific mutations using the amplification refractory mutation system (ARMS). This multiplex ARMS approach was standardized using DNA samples with known mutations for beta-thalassemia in those of Asian (Southeast Asian, Chinese, and Asian Indian) and African-American descent. Specimens from African-American neonates were tested for two mutations (-88 and -29); Asian Indians for five mutations (IVSI-1, IVSI-5, codons (Cd) 41/42, Cd 8/9, and 619-bp deletion); Chinese, Taiwanese, and Southeast Asians for seven mutations (Cd 41/42, Cd 17, -28, IVSII-654, Cd 71/72, IVSI-5, and IVSI-1). We identified each of these beta-thalassemia mutations in multiplexed ARMS from positive control samples. We tested 25 anonymized dried blood specimens from neonates who had been diagnosed with beta-thalassemia and who also belonged to these ethnic groups. We detected a mutation specific to the neonate's ethnic group using the ARMS approach in nearly all specimens, and the results were confirmed by sequencing. Multiplexed ARMS for ethnic-specific beta-thalassemia mutations from the original newborn screening dried blood specimens is a rapid and efficient approach for diagnostic confirmation.

Asian People↗

PubMed1985

Haplotypes and levels of fetal hemoglobin and G gamma to A gamma ratios in Mediterranean patients with thalassemia minor and major.

This study concerned the gamma chain composition of Hb F and the haplotypes of 44 patients with beta-thalassemia major or intermedia and many of their relatives. Seventeen patients came from Northern (Turkish) Cyprus, 12 from the Istanbul area, and 15 from Macedonia and Bulgaria. Analysis of the A gamma T-G gamma-A gamma I ratio was made by HPLC, while haplotyping involved seven restriction sites. Specific haplotypes were present in certain populations; haplotype I [1] is the dominant type among North Cypriot thalassemia patients. Numerous types were seen in the patients from the Balkan countries. A direct relationship between the A gamma to G gamma ratios and the haplotypes, which exists among black beta-thalassemia heterozygotes [3], was also observed among these Mediterranean patients, although such analyses were considerably complicated by extensive blood transfusion therapy. Haplotypes without the Hinc II restriction site within the psi beta gene were associated with lower G gamma values than those that had this polymorphic site. The A gamma T chain was observed in a small number of beta-thalassemia homozygotes and heterozygotes. Three thalassemia chromosomes with slightly different haplotypes and one normal chromosome with a related haplotype were associated with the gamma 75 Ile----Thr substitution. A few patients with a thalassemia intermedia were heterozygotes for beta-thalassemia with either haplotypes V or VII [1] while the "nonthalassemic" chromosome had a haplotype I, which is the most common "beta-thalassemic" haplotype among the Mediterranean population(s). Detailed analyses of this chromosome have not been completed.

Adolescent↗

PubMed1986

The effect of Hb F and alpha-thalassemia on the red cell indices in sickle cell anemia.

This study examines the effect of different levels of fetal hemoglobin (Hb F) and the presence or absence of genes for alpha-thalassemia on the red cell indices and degree of anemia among 102 patients with homozygous sickle cell disease (S/S) between the ages of 15 and 62 years. Patients were divided into those with an average Hb F of less than 10 gm/L ("low" Hb F group) and those with greater than 10 gm/L ("high" Hb F group). alpha-Thalassemia was assessed by restriction enzyme analysis of DNA by the Southern blotting technique. Homozygosity for the beta(s) gene was confirmed by restriction enzyme analysis of DNA using the enzyme Mst II. There were 51 patients with four alpha-globin genes, 28 of whom had "high" and 23 "low" Hb F levels. Fifty-one patients had alpha-thalassemia, 38 of whom were heterozygous and 13 homozygous for the 3.7 kb alpha-thalassemia deletion. Nine had "high" and 31 had "low" Hb F. Irrespective of alpha-globin genotype, patients in the high Hb F group had a higher mean Hb, Hct, MCV, and MCH than those in the low HB F group. In patients without alpha-thalassemia Hb F was positively correlated with MCV and MCH (p less than 0.001), patients with high Hb F levels having macrocytosis confirmed by microhematocrit studies. Patients with alpha-thalassemia had a lower MCHC than patients with four alpha-globin genes and this was not significantly affected by the level of Hb F. The combination of alpha-thalassemia and high levels of Hb F appears to result in a distinctive S/S phenotype that is similar to the type of S/S disease described in Southern India.

Adolescent↗

PubMed1993

Molecular characterization of beta-thalassemia in Egyptians.

We sought to determine the spectrum of mutations producing beta-thalassemia in Egypt using genomic PCR and a variety of mutation-screening procedures. Thirty-four beta-thalassemia and three Hb S/beta-thalassemia patients originating from different regions of Egypt were studied, and the causative mutation was found in 69 of 71 (97%) beta-thalassemia genes. Four mutations accounted for 78% of beta-thalassemia genes in this population; IVS-1, nt 110 (41%), IVS-1 nt 6 (13%), IVS-1, nt 1 (13%), and IVS-2, nt 848 (11%). The latter allele, a C-A mutation at the third nucleotide of an acceptor site consensus sequence, has been described previously only in one Egyptian, one Iranian, one Tunisian, and one Black American patient. Nine other alleles each accounted for 1-3% of beta-thalassemia genes. Among these was one codon 27 allele (Hb Knossos), two frameshift 106/107 alleles previously seen only in a Black American, and a rarely observed mutation in the distal promoter region of the beta-globin gene, -87 (C-A). Our results suggest that from a molecular genetic standpoint a beta-thalassemia prevention program based on carrier screening and prenatal diagnosis can be implemented in Egypt. In couples at risk for beta-thalassemia, the causative mutation should be identifiable in both members in 92% and in one member in the remaining 8%.

Base Sequence↗

PubMed2005

Vascular-type disruptive defects in fetuses with homozygous alpha-thalassemia: report of two cases and review of the literature.

BACKGROUND: The thalassemias are an inherited group of heterogeneous anemias in which one or more of the globin chains in the hemoglobin tetramer are absent. Fetuses with homozygous alpha-thalassemia, which is particularly prevalent in people of Southeast Asian extraction, experience deficient alpha-globin chain synthesis and cannot produce hemoglobin F (the primary fetal hemoglobin after 8 weeks' gestation). Instead, they produce an anomalous hemoglobin, hemoglobin Bart's, with an unusually high affinity for oxygen, leading to profound anemia and tissue hypoxia. METHODS AND RESULTS: Here we report on two fetuses with homozygous alpha-thalassemia who displayed structural defects of a vascular disruptive type. Both fetuses demonstrated limb anomalies, including terminal transverse limb deficiencies, and one fetus was found to have a brain malformation consisting of a neuronal migrational defect. The limb anomalies and suspected brain malformation were detected on prenatal ultrasound prior to confirmation of the diagnosis of alpha-thalassemia in one case; in the other case prenatal records were not available. While microcephaly, hydrocephalus, and retarded brain growth have been rarely reported in association with homozygous alpha-thalassemia, this is the first report of a true brain malformation in an affected fetus. Limb anomalies, on the other hand, appear to be more frequent. Recently, aggressive in utero and postnatal therapies for homozygous alpha-thalassemia have been attempted with some success. CONCLUSIONS: Our cases and those from the medical literature suggest that couples need to be counseled about the risks of congenital anomalies of a vascular disruptive type in affected fetuses. Furthermore, data from the literature suggests that in utero therapy may not significantly decrease these risks as such anomalies may be present prior to the institution of therapy. In addition, in hydropic infants with vascular disruptive defects, especially in those of Southeast Asian origin, homozygous alpha-thalassemia should be suspected as a likely etiology.

Adult↗

PubMed1992

The molecular basis of beta-thalassemia in Turkey.

By using oligonucleotide hybridization, restriction endonuclease analysis and direct sequencing of amplified genomic DNA, we have been able to characterize 18 different mutations in the beta-globin genes of 161 beta-thalassemia homozygotes and 107 beta-thalassemia heterozygotes from Turkey (429 beta-thalassemia chromosomes). Previous studies dealing with beta-thalassemia in Mediterranean countries have shown that, in most Mediterranean populations, only a few mutations are prevalent. In contrast, beta-thalassemia in Turkey does not seem to be associated with a few predominant mutations. The six most frequent alleles, IVS-I-110 (G----A), IVS-I-6(T----C), FSC-8 (-AA), IVS-I-1(G----A), -30(T----A) and FSC-5 (-CT), account for only 69.3% of the disease genes; indeed, all 26 mutations assayed represent 85.8% of the disease genes, confirming the considerable molecular heterogeneity of beta-thalassemia among Turks, and indicating the possible presence of rare, previously undefined, mutations in the population. Two mutations observed in this study, IVS-I-116 (T----G) and Cd44(-C), have not been reported in the Turkish population to date. Since preventive medical services, such as genetic counseling and prenatal diagnosis, are greatly improved by detailed knowledge of the molecular pathology of beta-thalassemia, we strongly believe that the presented data will facilitate the intended establishment of a prenatal diagnosis center, based on DNA analysis, in Turkey.

Alleles↗

PubMed1986

Alpha-thalassemia in Papua New Guinea.

A study of the distribution of alpha-thalassemia in Papua New Guinea (PNG) was carried out by DNA analysis. A total of 664 DNA samples were screened for alpha-thalassemia 2 and alpha-thalassemia 1 caused respectively by either deletion of one or both of the duplicated alpha-globin genes. alpha-Thalassemia 2 was detected in high frequencies in coastal and lowland regions where malaria has been holo- to hyperendemic but in low frequencies in non-malarious highland regions. The highest frequency was observed in the north coast of PNG. The distribution of alpha-thalassemia 2 seems to be in accordance with other conditions such as ovalocytosis and G6PD deficiency which are also prevalent in this population, suggesting that they may interact in protection against malaria. However, it appears to be negatively correlated with beta-thalassemia and alpha-thalassemia 1, the latter being extremely rare in this population. Analysis of the types and subtypes of the single alpha-globin gene deletion revealed a predominance of the -alpha 4.2 type in general, except in some regions in the south where the -alpha 3.7 type is prevalent. The -alpha 3.7 I subtype is the common form of the -alpha 3.7 deletion in the PNG mainland. The -alpha 3.7 III subtype, previously reported to be unique in Melanesians and Polynesians, was detected in an offshore island of PNG. However, this subtype is very rare in Melanesians from the PNG mainland.

Chromosome Deletion↗

PubMed1987

Different severity of homozygous beta-thalassemia among siblings.

Different degrees of severity of anemia are presented in three siblings with homozygous beta-thalassemia. II-1, the most severely affected one, is splenectomized and needs frequent blood transfusion, while II-4 has mild anemia and never receives transfusion. II-3 has moderate anemia and mild jaundice and hepatosplenomegaly. Restriction endonuclease DNA mapping revealed the alpha-thalassemia-2 genes in II-3 and II-4 and no alpha-thalassemia-2 haplotype in II-1. Furthermore, II-4, who is mildly affected, is homozygous for alpha-thalassemia-2 whereas II-3 is an alpha-thalassemia-2 heterozygote. These observations indicate that concomitant inheritance of alpha-thalassemia can decrease the severity of beta-thalassemia.

Chromosome Deletion↗