Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “THALASSEMIA”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources
PubMed2005

Thalassemia intermedia associated with complex interaction of Hb Beijing [alpha16(A14)Lys-->Asn] and Hb E [beta26(B8)Glu-->Lys] with a deletional alpha-thalassemia-1 in a Thai family.

A Thai family with a complex thalassemia syndrome caused by alpha- and beta-globin defects is described. The proband was a 14-year-old boy who had chronic hypochromic microcytic anemia. Hemoglobin (Hb) and DNA analyses demonstrated that he carried Hb Beijing [alpha16(A14)Lys-->Asn], Hb E [beta26(B8)Glu-->Lys] and alpha-thalassemia-1 (alpha-thal-1). Interaction of the alphaBeijing with the betaE globin chains in the proband leads to a new Hb variant, namely Hb E Beijing with different characteristics to both Hb E and Hb Beijing. Family studies showed that his father carried Hb Beijing and Hb E, whereas his mother was a simple alpha-thal-1 carrier. The genotype-phenotype relationship observed in this Thai family with complex hemoglobinopathies is presented and a simple DNA assay based on allele specific polymerase chain reaction (ASPCR) for detection of Hb Beijing is described.

Adolescent↗
PubMed1987

Molecular characterization of beta-thalassemia major and beta-thalassemia intermedia in China and Southeast Asia.

We have studied the spectrum of mutations producing beta-thalassemia (beta-thal) in South China and Southeast Asia in two groups of patients. In randomly selected patients with beta-thal major we characterized 78 beta-thal genes. In patients with beta-thal intermedia, 22 beta-thal genes were studied. The relevant mutation was characterized in all 78 genes of the first group, and 21 of 22 (96%) of mutant genes in the second group. Eight point mutations were found among the 100 genes studied. Of these eight alleles, four constituted 90% of the total. Prenatal diagnosis of beta-thalassemia in this region should be feasible by simplified techniques for direct detection of point mutations.

Asia, Southeastern↗
PubMed1986

Homozygous hemoglobin Knossos (alpha 2 beta 227(B9) Ala----Ser): a new variety of beta (+)-thalassemia intermedia associated with delta (0)-thalassemia.

Hb Knossos (beta 27 (B9) Ala----Ser) is a recently discovered hemoglobin variant endowed with beta-thalassemic properties (1,2) We present the first homozygous cases. The propositus, a 19-year-old man is originally from northeast Algeria, but is unrelated to other Algerians who have hemoglobin Knossos. He has a beta(+)-thalassemia intermedia syndrome, including microcytic, hypochromic anemia, enlargement of the spleen, and an increase in the number of reticulocytes. The reduction of beta-chain synthesis is pronounced (alpha/non alpha:2.76). Whole cells containing Hb Knossos have a dramatically low oxygen affinity (P50:38 mm Hg). The propositus also has homozygous delta(0)-thalassemia. The chromosome carrying these mutations is characterized by the DNA haplotype I.

Adult↗
PubMed1981

The effect of alpha-thalassemia on the expression of the beta-thalassemia/HPFH heterozygote in a black family.

A 2-yr-old black girl presented with a thalassemic clinical picture and was found to have nearly 100% fetal hemoglobin in her red cells. Pedigree analysis indicated that she was a heterozygote for the hereditary persistence of fetal hemoglobin gene and for a beta O-thalassemia gene. A brother, who also had nearly 100% fetal hemoglobin in his red cells, manifested, in contrast to his sister, no anemia and only minimal splenomegaly. Examination of the family's alpha-globin loci using the restriction endonuclease Eco Rl demonstrated that the brother had a single alpha-locus deletion that he had inherited from his mother. The mild clinical manifestations of this boy are consistent with the often expressed view that excess alpha chains may contribute significantly to the hematologic manifestation of beta-thalassemia.

Black People↗
PubMed1998

[Campaign for the detection of minor beta-thalassemia and prevention of major beta-thalassemia in the isle of Menorca. 10-year experience].

BACKGROUND: The high prevalence of betathalassemia minor and the presence of several cases of thalassemia major in Menorca (Spain) led us, ten years ago, to set up a population based prevention campaign, following the basic schedule of those already taking place in other areas, specially in Italy. PATIENTS AND METHODS: The target population was the children in the last year of mandatory school, when they are 13 to 14 years old. The campaign started in the school year 1986-1987 and in the 1995-1996 course we reached the tenth yearly campaign. The campaign was structured in three stages: the first one included all information and educational aspects; the second step corresponded to blood sampling and detection of carriers; finally, results were reported to the individuals and genetic counseling was given. For evaluation purposes, we have monitored participation rates, the proportion of detected carriers which present to haematology visit and the trend in the proportion of carriers which previously knew their status. RESULTS: A total of 8,591 children were screened, accounting for a 83.8% participation rate. The observed prevalence was 26.7/1000 (95% CI, 23.5-29.9/1000). We also detected 9 cases of alfathalassemia and 4 cases of deltabetathalassemia. CONCLUSIONS: Our results show that participation rates may be reached through school screening campaigns for thalassemia. After ten years of campaign, the number of not previously known cases has become small, indicating that the campaign screening to relatives of detected carriers and a higher consciousness level in the general population have given the expected effect. In the last 14 years, not a single homozigote case has been born, although we cannot conclude that this has been only due to the campaign.

Adolescent↗
PubMed2005

Adult onset of a Thalassemia intermedia genotype in association with a -alpha-3.7 homozygosity. Hb G-Accra [beta73(e17)Asp-->Asn] in combination with beta- and alpha-thalassemia in the same family.

We present the case of a 39-year-old male of mixed Black and Chinese Surinamese origin referred because of abdominal pain and extreme tiredness. The patient reported that he had received a single blood transfusion in his youth and presented at intake with a severe microcytic hypochromic anemia. A chest X-ray and computer tomography (CT)-scan revealed bilateral mediastinal lymphadenopathy and interstitial infiltrates. Elevated Hb F (80%) and an unbalanced synthesis ratio (beta/alpha = 0.18) were compatible with severe beta-thalassemia (thal) intermedia. DNA analysis revealed a double heterozygoty for the -88 (C-->T) and the IVS-II- 654 (C-->T) mutations in the presence of a homozygosity for the -alpha3.7 deletion. The two daughters of the proband were both heterozygous for the IVS-II-654 (C-->T) mutation and the -alpha3.7 deletion. The youngest daughter also carried the Hb G-Accra [beta73(E17)Asp-->Asn] mutation, inherited from the mother. Hb G-Accra, a mutant of presumed Ghanaian origin, described as non pathological in the carrier, is reported for the first time in combination with a severe fbeta(+)thal. The molecular background, haplotype of the mutations and a new A--> polymorphism at -309, 5' to the G(gamma) romoter, are reported.

Adult↗
PubMed1996

Globin mRNA in beta-thalassemia heterozygotes with different beta-thalassemia alleles and in heterozygotes for hereditary persistence of fetal hemoglobin.

Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to determine the alpha 2/alpha 1-, alpha/beta-, and gamma/beta-mRNA ratios in subjects with beta-thalassemia (beta-thal), hereditary persistence of fetal hemoglobin (HPFH), and normal adults. The alpha- and beta-globin gene mutations were characterized with gene mapping, PCR, and DNA sequencing. The average alpha 2/alpha 1-mRNA ratio was the same in normal adults and beta-thal heterozygotes with four alpha-globin genes (2.61-2.63) or with an alpha-thal-2 trait (1.48-1.55). The average alpha/beta-mRNA ratios were 4.47 and 3.84 in normal adults with four alpha-globin genes and with alpha-thal-2 trait (-alpha/alpha alpha), respectively. There was an increase of approximately 50% in beta-thal heterozygotes with transcriptional mutants [-88 (C-->T) and -29 (A-->G)] with lower values (approximately 25%) in those with alpha-thal-2 trait (-alpha/alpha alpha). High alpha/beta ratios were also observed for heterozygotes for nonsense or frameshift mutants located in exon 1 or exon 2. Increases of approximately 150-165% were seen in subjects with RNA processing defects; an exception was the IVS-1-110 (G-->A) mutation with a normal value in the heterozygote. The increases were also less pronounced in heterozygotes for the codon (CD) 121 (G-->T) mutation and the CDs 134-137 insertion/deletion. Normal alpha/(gamma + beta) values were seen in 3 heterozygotes each with a different deletion involving part of the beta-globin gene. The presence of the silent beta-thal allele, -101 (C-->T), in trans to a CD 8 (-AA) allele has a minor effect on the alpha/beta-mRNA ratio. The alpha/beta-mRNA ratio in HPFH heterozygotes was approximately 145% of normal, but with a gamma-mRNA level of 35.4-44.7% the calculated alpha/(gamma + beta) ratio became as in normal adults. The RT-PCR methodology appears useful in expression studies in beta-thal (and HPFH) and values of mRNA appear to correspond to the type of prevailing mutation(s) and concomitant alpha-thal.

Adolescent↗
PubMed1994

Molecular characterization of alpha-thalassemia determinants, beta-thalassemia alleles, and beta S haplotypes among Kuwaiti Arabs.

Using amplification, allele-specific oligonucleotide (ASO) hybridization and DNA sequencing we have documented the molecular basis of 64 alpha- and 123 beta-thalassemia (thal) chromosomes, and the haplotypes of 18 beta S chromosomes from patients followed in three hospitals in Kuwait. Of the 30 chromosomes from 15 patients with Hb H disease, 26 (86.7%) carried the polyadenylation (poly A) signal mutation (AATAAA-->AATAAG) in the alpha 2-globin gene, 3 (10%) had the -alpha (3.7 kb) deletion, and 1 (3.3%) had the pentanucleotide deletion in the 5' IVS-I splice junction (alpha-5nt alpha). As many as 12 different beta-thal mutations were identified; 6 Mediterranean alleles [IVS-II-1 (G-->A), IVS-I-6 (T-->C), codon (CD) 39 (C-->T), IVS-I-110 (G-->A), CD 8 (-AA), and IVS-I-1 (G-->A)] were present in 79 (64.2%) of the chromosomes tested. Four East Indian alleles [IVS-I-5 (G-->C), IVS-I 3' end -25 nt deletion, CDs 8/9 (+G), and 619-bp deletion] were found in 31 (25%), and the two Kurdish/Iranian alleles [CD 44 (-C) and CDs 36/37 (-T)] were found in 13 (10.6%) chromosomes. Fourteen beta S chromosomes carried haplotype No. 31 (Saudi Arabia/India); 3 had haplotype No. 19 (Benin), and 1 was a hybrid with haplotype No. 31-specific characteristics in the locus control region hypersensitive site-2 (LCR-HS-2), and haplotype No. 19-specific mutations in the 5' flanking region of the G gamma-promoter. The patient homozygous for haplotype No. 19 was a Jordanian, while the others were Kuwaiti Arabs. The latter appear to be fairly homogeneous in terms of the prevalent alpha-thal determinants and beta S-haplotypes, but there is considerable heterogeneity of their beta-thal alleles. This has implications for genetic counseling and prenatal diagnosis programs.

Anemia, Sickle Cell↗
PubMed2001

[The prevalence of beta-thalassemia heterozygotes compound alpha-thalassemia in Guangdong district].

OBJECTIVE: To investigate the prevalence of beta-thalassemia (beta-thal) heterozygotes compound alpha-thal in Guangdong area. METHODS: alpha-thal 1 genes were amplified in 500 beta-thal carriers diagnosed by reverse dot blotting (RDB) using gap-PCR method, alpha-thal 2 genes were detected in 400 of the 500 beta-thal carriers using Southern blotting with alpha-globin DNA probe and restrict endonuclease zymogram analytical method. RESULTS: Forty three alpha-thal-1(alpha alpha/- -SEA) cases were identified in the 500 beta-thal traits, and 26 alpha-thal 2 including 17 rightward deletion (alpha alpha/- alpha 3.7) and 9 leftward deletion(alpha alpha/-alpha 4.2) cases were identified in the 400 beta-thal traits. CONCLUSION: The prevalence of beta-thal heterozygote carrying alpha-thal-1 gene was 8.6% and that of beta-thal heterozygote carrying alpha-thal-2 gene was 6.5% (4.2% rightward deletion and 2.2% leftward deletion).

Adult↗
PubMed1989

Molecular basis of beta-thalassemia in Thailand: analysis of beta-thalassemia mutations using the polymerase chain reaction.

beta-Thalassemia mutations in 71 chromosomes of Thai patients from the northeast, the middle and the south of the country were investigated using dot blot hybridization of PCR (polymerase chain reaction)-amplified DNA with allele-specific oligonucleotide probes. Eight different known molecular defects were detected, at different frequencies. There was an amber mutation in codon 17, a C-T transversion at position 654 of IVS-2, a frameshift mutation between codons 71 and 72, an A-G transition at nucleotide -28 within the TATA box (known as Chinese mutations), a G-T transversion at position 1 of IVS-1 (an Indian mutation), a 4 bp deletion in codons 41/42 and a G-C transversion at position 5 of IVS-1 (described as both Chinese and Indian mutations) and a Thai original mutation, an ochre mutation in codon 35. Analysis of the three unknown alleles by DNA sequencing of the cloned DNA fragment amplified by PCR revealed an A-G substitution at the second position of the codon for amino acid 19 (AAC-AGC). The analytic approach used in the present study and the characteristic distribution of mutations in each region of Thailand will prove useful for setting up a prenatal diagnosis program.

Alleles↗
PubMed1992

Beta-thalassemia major resulting from a compound heterozygosity for the beta-globin gene mutation: further evidence for multiple origin and migration of the thalassemia gene.

We describe in a Japanese family beta zero-thalassemia resulting from a compound heterozygosity for a beta-globin gene mutation. One mutation is a C-to-T transition at IVS-2 nucleotide position 654 on the background of Mediterranean haplotype IX. Another mutation is a G-to-A transition at IVS-2 nucleotide position 1, associated with a novel haplotype XI. The occurrence of these mutations on various chromosomal backgrounds provides strong evidence for an interplay of gene migration, interallelic gene conversion, and multiple origins of the same mutation.

Adult↗
PubMed1984

A leftward deletional alpha+ thalassemia found in East Sicily in conjunction with heterozygous beta-thalassemia.

Two types of alpha+ thalassemia (-alpha l) have been described, respectively termed leftward and rightward, which correspond to nonhomologous crossing-over in different homology zones X and Z within the alpha-globin gene cluster. Up to now the leftward type has been described only in Asiatic populations, whereas the rightward type is universally distributed. We report here a first case of leftward deletion observed in a Sicilian male. This raises the question of an identical or not crossing-over event.

Aged↗
PubMed2000

Epidemiological situation and treatment of patients with thalassemia major in Germany: results of the German multicenter beta-thalassemia study.

At present, about 300 patients in Germany suffer from thalassemia major. In 1990, a multicenter study was introduced to identify all thalassemic patients in Germany as well as to establish a uniform therapy protocol, including follow-up diagnostic procedures. After 6 years of study, the data of 203 patients were analyzed. The majority originate from endemic regions around the Mediterranean Sea. The median age of the patients is 13.8 years (range 1-37.5 years). At present, about 20% of the patients are older than 21 years. Regarding transfusion therapy, a shortening of the average transfusion interval to 3 weeks in most cases occurred. Throughout the entire period, median baseline hemoglobin concentrations of 10.0 g/dl were observed. The evaluation of serum ferritin levels revealed considerable differences, depending on the patients' age. Thalassemic patients in the first decade of life generally presented with good therapeutic results; serum ferritin levels were below 1800 ng/ml in 76/102 patients (75%) upon entry into the study. In contrast, 51/98 patients (52%) older than 10 years had ferritin levels above 2500 ng/ml. More than half of all treated patients presented with siderotic complications such as cardiac disease in 20/157 (13%), liver disease in 32/157 (21%), impaired glucose metabolism in 22/157 (14%), hypogonadism in 39/66 (59%), and hypothyroidism in 38/157 (24%) who were under treatment at the time of first survey. Since the situation concerning siderosis and the lack of compliance proved to be particularly difficult with adolescent patients, further efforts should concentrate on this age-group.

Adolescent↗
PubMed2001

Antioxidant defense status of red blood cells of patients with beta-thalassemia and Ebeta-thalassemia.

Anemia in beta-thalassemia is caused by a combination of ineffective erythropoiesis and premature hemolysis of RBC in the peripheral circulation. Excess of the alpha-globin chain present in beta-thalassemic RBC is mainly responsible for oxidative damage of erythrocyte membrane protein. The activities of glucose-6-phosphate dehydrogenase, glutathione reductase, glutathione peroxidase, and glutathione-S-transferase, and the catalytic activity of catalase and superoxide dismutase, and the concentrations of non-enzymic antioxidants such as reduced glutathione were measured to estimate the status of the antioxidant defense system in the erythrocytes for protection against oxidative stress. The extent of lipid peroxidation was also estimated in thalassemic erythrocytes. Significantly lower activities of reduced glutathione indicate the cell to be in a pro-oxidant state and decreased activity of catalase favors hydrogen peroxide-mediated lipid peroxidation in beta-thalassemic and Ebeta-thalassemic RBC.

Antioxidants↗
PubMedDate not supplied

[Hemoglobin C -- beta-thalassemia disease and homozygous beta-thalassemia in a black African family (author's transl)].

The study of a Malian family has allowed to prove existence of two types of beta-thalassemia genes: the beta0 gene which suppresses the synthesis of the beta chain into cis position and the beta+ gene which slows down only partially this synthesis. The difference between this two genes has been possible owing to the hemoglobin C found in this family and induced by the betaC mutated gene. The segregation of the four genes betaA, betaC, beta0 thal, and beta+ thal. has allowed to compare all the possible phenotypes deriving from the combinations by two of these allelic genes.

Alleles↗
PubMed2005

Compound heterozygosity for unstable hemoglobin Genova and beta(o)-thalassemia associated with early onset of thalassemia major syndrome.

We described the case of an infant with compound heterozygozity for a b0-thalassemic mutation and Hemoglobin (Hb) Genova, an unstable Hb variant. He has required regular transfusions as early as the second month of life and since then, behaves like a thalassemia major patient. This association leads to the most severe clinical course involving an unstable variant, reported so far.

Blood Transfusion↗
PubMed2005

Abnormalities in lung function among multiply-transfused thalassemia patients: results from a thalassemia center in Malaysia.

The aim of this study was to: (1) determine the prevalence and patterns of lung dysfunction among transfusion dependent thalassemics; (2) determine the associated factors that might contribute to this problem. This was a cross-sectional study involving 66 patients with transfusion dependent thalassemia aged 10 years and above. All patients underwent physical examination, standardized pulmonary function tests including spirometry, lung volume, and the carbon monoxide diffusion capacity. A restrictive pattern of lung dysfunction was observed in 22 patients (33.3%) and none showed the presence of obstructive ventilatory impairment. A reduction in the carbon monoxide diffusion capacity (DLCO) was seen 87.9% of the patients, including 7.6% who had evidence of hypoxemia. Ten patients showed a reduction in the FEF25-75% although they did not fulfil the criteria for small airway disease. No correlation was found between lung dysfunction and serum ferritin levels in the patients. Restrictive lung dysfunction and diffusion impairment were the predominant abnormalities found in our cohort of patients.

Adolescent↗
PubMed2006

Common alpha-thalassemia deletions in transfusion-dependent thalassemia patients in the Southeast Asia region of Myanmar.

Screening of 3 common alpha-thalassemia (thal) deletions (-alpha3.7, -alpha4.2 and --SEA) in Southeast Asia was done by polymerase chain reaction in 170 unrelated Myanmar thal patients receiving transfusions. Thal deletions were detected in 27 patients (15.9%) as: (1) alpha-thal-2 (-alpha3.7/alphaalpha) in 12 heterozygous or hemoglobin (Hb) E-beta-thal cases; (2) alpha-thal-1 in 7 patients (2-alpha3.7/-alpha3.7 and 5 --SEA/alphaalpha); and (3) Hb H (-alpha3.7/--SEA) in 8 patients. The latter 15 alpha-thal-1 and Hb H patients had no beta-thal mutations and represented 8.8% of the overall patients seeking transfusion for refractory anemia in Myanmar. This is the first description of alpha-thal in Myanmar from the molecular aspect, and its clinical and racial heterogeneity are described and discussed.

Adolescent↗