Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied a Portuguese family with a dominant beta-thalassaemia trait that was present in one member of each of three generations. It was characterized by a moderate anaemia, microcytosis and hypochromia, anisopoikilocytosis, Heinz body formation in peripheral red cells, splenomegaly, and a blood transfusion requirement during pregnancy. Sequence analyses of amplified DNA detected a deletion of (G) TG.GCT.GGT.GT(G) at codons 134-137 (Val.Ala.Gly.Val) and the insertion of (G)GC.AG(G) (Gly.Arg) at the same location. Thus, the resulting beta chain has an abnormal structure only at codons 134-137 and is two residues shorter than the normal 146 residues. This chain could not be detected in circulating red cells and must be degraded rapidly by proteolysis because the Heinz bodies consisted mainly of alpha chains.
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PMID:Dominant beta-thalassaemia trait in a Portuguese family is caused by a deletion of (G)TGGCTGGTGT(G) and an insertion of (G)GCAG(G) in codons 134, 135, 136 and 137 of the beta-globin gene. 165 62

Characterization of beta-thalassemia mutations were attempted for 29 Japanese families clinically diagnosed as having beta-thalassemia. Following the identification of a mutation by cloning and sequencing, all families were screened for this particular mutation, using biotinylated allele-specific oligonucleotide probes. Seven different mutations were detected in 17 families: Six families had the frameshift mutation at codons 41/42, resulting from a 4 nucleotide deletion (TTCTTT----TT); four had the deletion at codons 127/128 (CAGGCT----CCT); and three had the TATA box mutation at nucleotide -31 (A----G). Four additional families had mutations at codon 24 (GGT----GGA), codon 26 (GAG----AAG), IVS-II-654 (C----T) and codon 110 (GTG----CCG), respectively. The newly discovered deletion mutation at codons 127/128, and mutations at nucleotide -31, and at codon 110 are peculiar to Japanese, and have not been found in any other ethnic group. The haplotypes of the beta-globin gene cluster were also determined. Some of the haplotypes and beta-thalassemia mutations are identical to those reported in the Chinese population. However, it is noteworthy that nearly half of the beta-thalassemia mutations were unique to Japanese.
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PMID:Characterization of beta-thalassemia mutations among the Japanese. 263 67

A beta+-thalassemia mutation at codon 24 (GGT----GGA) was discovered in a Japanese; this is the third type of beta-thalassemia found in this population. The case, as well as the data from DNA sequencing analysis, are presented.
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PMID:A beta+-thalassemia (codon 24, GGT----GGA) found in a Japanese. 320 9

A beta+-thalassemia globin gene was isolated from the genome of a Black individual by molecular cloning. DNA sequence analysis revealed only a single difference between this gene and the normal human beta-globin gene--adenine is substituted for thymine in the third position of codon 24. Codon 24 in both the normal gene (GGT) and the beta+-thalassemia gene (GGA) encodes glycine. The function of this beta+-thalassemia gene was compared to the function of the normal human beta-globin gene in monkey kidney cells by using plasmid expression vectors. The codon 24 substitution activates a 5' splice site that involves the guanine-thymine dinucleotide present in codon 25, 16 nucleotides upstream from the normal exon 1-intron I boundary. The splice, involving the abnormal 5' site in codon 25, is completed with the normal 3' splice site at the end of intron I. This splicing abnormality leads to a 75% decrease in the accumulation of normally processed beta-globin mRNA, thereby causing the beta+-thalassemia phenotype.
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PMID:"Silent" nucleotide substitution in a beta+-thalassemia globin gene activates splice site in coding sequence RNA. 657 78

Women with transfusion dependent thalassaemia suffer from failure of pubertal growth and delayed onset of menarche with amenorrhea, anovulation and infertility. With improved pediatric and hematological care is now possible, for patients with b thalassaemia, to achieve a pregnancy. Pre-pregnancy assessment included checks for hypothyroidism and diabetes, for hepatitis B and C, human immunodeficiency virus, Rubella, cardiac functions, liver functions by estimating aspartate and alanine aminotransferases, gamma-glutamyl transpeptidase, alkaline phospatase, and total plasma proteins. The frequency of blood transfusion needed to be increased in order to maintain the hemoglobin concentration above 10 g/dl. Desferroxamine must be stopped as soon as pregnancy is diagnosed continuing the administration of the folic acid supplements throughout pregnancy. Desferroxamine will be resumed after delivery. The safety of iron chelation with desferroxamine during the periconceptional period and pregnancy has not yet been established. Some animal studies have shown skeletal anomalies; other published studies report seven women with b thalassaemia major who became pregnant while taking desferroxamine: all the women had normal babies. The mode of delivery is usually vaginal, while Cesarean section is performed in those cases with pre-eclampsia, fetal distress, cephalopelvic dysproportion, slow progression of labor, as in women without thalassaemia. In conclusion, with the advent of regular blood transfusion associated with iron chelation therapy, pregnancy in b thalassaemia can be safe for mothers and their babies with appropriate care.
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PMID:[Pregnancy in women with thalassaemia]. 1139 93

Hepatitis C virus (HCV) infection is a common cause of liver disease in thalassemia major patients in Western, especially Mediterranean, countries. Its significance in thalassemic patients from Southeast Asia has not been critically evaluated. In this report, we describe our study of the prevalence of HCV infection among Thai patients with thalassemia. The relationships of the infection to blood transfusion and the infection's effects on liver function have also been determined. Of the 104 patients studied, 21 (20.2%) tested positively by enzyme immunoassay for anti-HCV antibody, whereas only 2 patients (2%) had the hepatitis B surface antigen. There was no significant relationship between the presence of anti-HCV antibodies and the number and frequency of blood transfusions. In fact, 2 patients (10%) who tested positive for anti-HCV antibodies had never received transfusions. Patients with anti-HCV antibodies had significantly abnormal liver functions, such as higher levels of serum aspartate aminotransferase (SGOT) and alanine aminotransferase (SGPT) and lower levels of serum albumin, compared with patients without anti-HCV antibodies (P = .021, .017, and .004, respectively). However, there were also significant correlations between iron status as indicated by transferrin saturation or serum ferritin levels and SGOT, SGPT, and gamma-glutamyltransferase (GGT) levels. Moreover, abnormal liver function as represented by elevated levels of SGOT, SGPT, GGT, and serum alkaline phosphatase was observed more frequently in patients with iron overload than in patients with a lower degree of iron burden. The presence of HCV did not alter the effects of iron overload on liver function. The findings suggest that both HCV and iron overload are the main causes of abnormal liver function in Thai patients with thalassemia. The treatment of both problems, if coexisting in patients with thalassemia, is required to prevent progression to chronic liver disease.
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PMID:Prevalence and clinical significance of hepatitis C virus infection in Thai patients with thalassemia. 1468 98

A study on thalassemia intermedia and major patients in Jakarta was initiated to obtain a comprehensive picture of metabolic dysregulation, iron overload, oxidative stress, and cell damage. Data are presented from a group of 14 transfusion-dependent patients in an age range of 11-25 years (T) and another group of 9 frequently transfused (for at least 15 years) patients aged 17-30 years (L). A third group comprised 6 patients (aged 7 to 14 years) who had not yet obtained transfusions (N). The 21 controls (C) were voluntary students without diagnosis or clinical signs of thalassemia up to 30 years of age. The study was approved by the Ethical Clearance Board of the Medical Faculty and all blood samples from controls and patients were obtained on fully informed consent. Levels of antioxidants (vitamins A, C, E and beta-carotene) and reactive thiols are considerably decreased in transfused patients, whereas signs of iron overload and cell damage are increased (serum iron, ferritin, transferrin saturation, SGOT, SGPT, gamma-GT, bilirubin). Results can be summarized that non-transfused thalassemia intermedia patients exert slight signs of oxidative stress, and increased hemoglobin degradation but no significant indication of tissue or cell damage. This picture differs considerably from transfusion-dependent thalassemia major patients: highly significant decrease in antioxidants and thiols and tremendous iron overload and cell damage. The picture is even worsened in long-term transfused patients. Iron chelation after transfusion is not sufficient in Indonesia, because it is normally (with few exceptions) applied only once together with transfusion. Hence, one major reason of the bad condition of transfusion-dependent thalassemia patients in Indonesia appears to be frequent transfusions (on the average one per month) and insufficient chelation of one treatment per month together with transfusion.
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PMID:Iron status and oxidative stress in beta-thalassemia patients in Jakarta. 1475 77

The proband is an elderly woman (79 years of age) of Surinamese-Hindustani origin, suspected of being a carrier of a nondeletional alpha-thalassemia (thal) because of a moderate microcytic hypochromic anemia at normal ferritin levels and in the absence of any other alpha-thal deletions. Sequence analysis revealed a silent mutation (GGC-->GGT) at codon 22 of the alpha2-globin gene. This mutation generates a splice donor site consensus sequence (GGTGAG) between codons 22 and 23. The abnormally spliced mRNA leads to a premature termination between codons 48 and 49. The presence of a downstream intron may induce the intracellular degradation of the affected mRNA, a pathway known as nonsense mediated decay (NMD), and this explains the alpha(+)-thal phenotype observed in the patient. The codon 22 (GGC-->GGT) transition described in this report is the first mutation creating a splice donor site in one of the alpha-globin genes.
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PMID:An alpha-thalassemia phenotype in a Dutch Hindustani, caused by a new point mutation that creates an alternative splice donor site in the first exon of the alpha2-globin gene. 1548 95

We report the hematological and molecular characterization of compound heterozygosity for hemoglobin (Hb) Hope/Hb E and double heterozygosity for Hb Hope/ alpha-thalassemia 2 found in 2 unrelated Thai individuals. The first proband presented with slight anemia and mild hypochromic microcytosis. Routine cellulose acetate Hb electrophoresis at pH 8.6 revealed in addition to Hb E another variant migrating slightly more anodic to Hb A. On cation exchange high-pressure liquid chromatography, the variant was eluted in the amount of 60.9% after Hb E The same abnormal Hb was found in a second family in which the proband and her younger sister were both double heterozygotes for this Hb variant and deletional alpha-thalassemia 2, whereas an older sister was a pure carrier of the variant. The amounts of this variant were found to be 34.9%, 35.4%, and 38.3% in the proband, her younger sister, and her older sister, respectively. Direct DNA sequencing of the amplified beta-globin genes of both probands identified the GGT (Gly)-GAT (Asp) mutation at codon 136 corresponding to Hb Hope. beta-Globin gene haplotype analysis demonstrated that all the Thai betaHope genes were associated with the same haplotype, (+ - - - - + +), indicating a single origin of this variant in Thailand. A simple method based on allele-specific polymerase chain reaction for accurate diagnosis of the Hb Hope is described.
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PMID:Molecular and hematological characterization of hemoglobin Hope/hemoglobin E and hemoglobin Hope/alpha-thalassemia 2 in Thai patients. 1569 92

Hb Hope [beta136(H14)Gly --> Asp (GGT --> GAT)] has been found alone or in combination with other globin gene mutations in several African-American families, as well as in Japanese, Thai, Laotian, Cuban and Mauritanian families. We report the hematological and molecular characteristics of a heterozygous association of Hb Hope with beta0-thalassemia (thal) in a Spanish patient, in whom the level of expression of abnormal hemoglobin (Hb) by cation exchange high performance liquid chromatography (HPLC) and electrophoresis suggested initially a homozygous expression of the abnormal Hb, although sequencing of the polymerase chain reaction (PCR)-amplified beta-globin gene demonstrated a heterozygous genotype for Hb Hope. To the best of our knowledge, this is the first description of a case of Hb Hope in a Spanish family.
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PMID:Heterozygous Hb Hope [beta136(H14)Gly --> Asp] in association with heterozygous beta0-thalassemia with apparent homozygous expression, in a Spanish patient. 1654 Apr 15


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