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 present a case of beta-thalassemia intermedia involving a 13-year-old boy of Northern European descent. His mother, father and older sister have normal hematologic indices. Molecular studies demonstrate that the proband carries a novel mutation of the beta-globin gene initiation codon (ATG-->AAG) which should give rise to beta(0)-thalassemia trait. The possibility of non-paternity was excluded, indicating that the novel mutation was the result of a de novo event. A review of the literature indicates that mutations involving the beta-globin gene initiation codon can give rise to a more severe phenotype than is generally associated with most other beta(+) or beta(0) mutations.
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PMID:De novo mutation of the beta-globin gene initiation codon (ATG-->AAG) in a Northern European boy. 937 31

beta-Thalassemia mutations in 221 chromosomes of unrelated southern Thai patients were analyzed. Using dot blot hybridization of PCR amplified DNA with 15 allele specific oligonucleotide probes for beta-thalassemia mutations 196/221 (89%) of the alleles were characterized. Ten mutations were identified, of which six [codon 41/42 (TTCTTT-TT), IVS1 nt5(G-C), codon 19 (AAC-AGC), codon 17 (AAG-TAG), IVS1 nt1(G-T), -28 TATA (A-G)], accounted for 85%. Among the 25 uncharacterized alleles, 15 were analyzed by automated fluorescent DNA sequencing of the whole beta-globin gene with normal results in 7 alleles. Four mutations, previously described were detected in 8 alleles. They were a G-A at IVS1 nt1 in one heterozygote, a G-T at IVS1 nt1 in one heterozygote, codon 15 (TGG-TAG) in two heterozygotes and poly A(AATAAA-AATAGA) in two homozygotes. The polyadenylation mutations, previously demonstrated in the Malaysian population have been first detected in Thailand. It is remarkable that the IVS1 nt1 (G-A) mutation, previously reported in the Mediterranean population has been found only in the south of Thailand. This mutation was probably imported from Portugal. In former times the Portuguese had settled in Phuket in southern Thailand. In order to find a causative mutation in the rest of 7 true unknowns we performed direct DNA sequencing of the core fragments of the beta-Locus Control Region Hypersensitive Sites (LCR HS) 2,3 and 4 in these 7 samples. DNA sequencing of HS2 and HS3 fragments showed normal results. The heterozygote A/G was present in the palindromic sequence of the LCR HS4 (TGGGGACCCCA) in 6 beta-thalassemia samples. The same heterozygote A/G was found in 5/12 normal subjects. The allele frequency of A (0.79) is obviously higher than that of G (0.21). This could be due to the stability of the palindromic structure. When an A is in the middle of the palindromic sequence, the hairpin structure is formed. In contrast the hairpin structure disappears when a G is in the middle of the palindromic sequence. This structure is not further symmetric and may not be so stable as the hairpin structure. beta-Thalassemia mutations in southern Thailand are very heterogeneous and their distribution is different from other parts of the country.
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PMID:Analysis of beta-thalassemia mutations and beta-locus control region hypersensitive sites 2, 3 and 4 in southern Thailand. 964 Jun 13

Hemoglobin (Hb) E is the most common Hb variant among Southeast Asian populations. The mutation in codon 26 (GAG to AAG) of the beta-globin gene (beta E) induces alternative splicing, resulting in the production of normally and aberrantly spliced beta-globin mRNA. Compound heterozygosity for beta-thalassemia and HbE, beta-thalassemia/HbE disease, could lead to a severe thalassemia phenotype. Repression of aberrant splicing from the beta E mutation could ameliorate the severity in such patients. We showed that the aberrant splicing was partially repressed in cells treated with antisense oligoribonucleotide targeted to the aberrant 5' splice site. The maximum effect of the antisense oligoribonucleotide was observed at a concentration of 0.4 mumol/L, 36 hours after the treatment in our experiment. We also analyzed the effect of the transient and stable expression of SF2/ASF on aberrant splicing in cells expressing the beta E-globin gene. Partial repression of the aberrant splicing was also observed in both expression systems. Our results imply that antisense oligoribonucleotide treatment and SF2/ASF expression are possible therapeutic applications for beta-thalassemia/HbE disease.
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PMID:Repression of aberrant splicing in human beta-globin pre-mRNA with HbE mutation by antisense oligoribonucleotide or splicing factor SF2/ASF. 1097 5

The high prevalence of beta-thalassemia in Southeast Asia is a major public health problem. Development of genetic counseling and prenatal diagnosis programs is a priority. To provide the groundwork for such programs in South Vietnam, we determined the spectrum of beta-thalassemia mutations in 35 severely affected patients and their relatives. We identified six different beta-thalassemia alleles (five beta(0) and one beta(+) mutations), in addition to the common mutation at codon 26 (GAG --> AAG) responsible for Hb E. These data provide insights into the distribution of beta-thalassemia alleles in the Vietnamese population.
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PMID:Molecular analysis of beta-thalassemia in South Vietnam. 1157 Jul 23

A 30-year-old female who is homozygous for a Hb E-like abnormal hemoglobin and her immediate relatives were studied. Clinical examination of the proband revealed no abnormality. Routine hematological analysis showed that her hemoglobin level was 12 g/dL, MCV 82 fL, MCH 28 pg, RDW 15%. DNA sequence analysis indicated the presence of a G-->A substitution at codon 22 corresponding to an abnormal hemoglobin, namely Hb E-Saskatoon [beta22(B4)Glu-->Lys (GAA-->AAA)]. Absence of any abnormalities in clinical and routine hematological investigations of the homozygous patient indicated that the phenotypical expression of the Hb E-Saskatoon is very mild. Using a reverse transcription-polymerase chain reaction technique, the alpha/beta and betaX/betaA-mRNA (X = Hb E-Saskatoon) ratios were determined. Normal alpha/beta and betaX/betaA-mRNA ratios were found in the homozygous patient and in all heterozygotes, indicating that the respective mutation did not alter the stability of the mRNA. FokI restriction enzyme analysis of the polymerase chain reaction products obtained from the genomic DNA and/or beta-globin mRNA made it possible for rapid diagnosis of Hb E-Saskatoon, and for its differentiation from Hb E [beta26(B8)Glu-->Lys (GAG-->AAG)]. Analysis of the restriction fragment length polymorphism (RFLP) in the beta-globin gene complex of the index patient and of another unrelated family with a compound heterozygosity for Hb E-Saskatoon and beta-thalassemia revealed that the Hb E-Saskatoon mutation shared a common allele.
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PMID:Homozygosity for Hb E-Saskatoon [beta22(B4)Glu-->Lys] in a Turkish patient. 1179 74

Korea is in the low-prevalence area of beta-thalassemia and the Korean population has relatively homogenous racial characteristics. Recently, we identified some causative mutations of the Korean beta-thalassemia patients. In order to elucidate the genetic background of beta-thalassemia alleles in Koreans, we determined the restriction fragment length polymorphism (RFLP)-haplotype and framework (FW) in nine beta-thalassemia chromosomes of five different causative mutations by PCR-based method and family linkage study. The result that the haplotype and the framework linked to the initiation codon ATG-->AGG mutation were -+-++-+ and FW3A, respectively, in all of three families in this study suggests a common origin of this mutation at least in Koreans. A novel beta-thalassemia mutation, codons 89/90 -TG, showed discrepancy between -++--++- and FW1, which could be explained by gene conversion. A case of codons 8/9 +G frameshift mutation had +----++ and FW1. The linkage of the two beta-thalassemia mutations, codon 17 AAG-->TAG and codons 41/42 -TTCT, with specific haplotypes and frameworks common to the Koreans and the neighboring countries suggests that those mutations are influenced by the genetic flow from the south China.
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PMID:RFLP haplotypes of beta-globin gene complex of beta-thalassemic chromosomes in Koreans. 1217 41

Hemoglobin (Hb) Korle-Bu (beta73; Asp-Asn) is the most frequent of the rare beta-chain variants in the population of West Africa whereas Hb E (beta26; Glu-Lys) is common among the Southeast Asian population. We report a hitherto undescribed condition in which these two beta-chain variants co-segregate. The proband was a 19-year-old Thai pregnant woman in her second trimester of pregnancy who visited our thalassemia screening unit. Cellulose acetate electrophoresis and high-performance liquid chromatography (HPLC) analysis of Hb detected one abnormal Hb in addition to the Hb E. Analysis of DNA sequences revealed a GAT-AAT mutation at codon 73 in trans to a GAG-AAG mutation at codon 26 of the beta-globin gene. Polymerase chain reaction (PCR) analysis of the alpha-globin gene cluster of the patient detected a 3.7-kb deletional alpha-thalassemia 2. Family study identified that her mother had the same genotype and her father was a simple Hb E carrier. The hematological data of these unusual cases of hemoglobinopathy are presented and compared with a simple heterozygote for Hb Korle-Bu found in another unrelated Thai family. beta-Globin gene haplotype linked to the Thai beta(Korle-Bu) and a simple DNA assay based on allele-specific PCR for rapid diagnosis of Hb Korle-Bu are also described.
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PMID:Compound heterozygosity for Hb Korle-Bu (beta(73); Asp-Asn) and Hb E (beta(26); Glu-Lys) with a 3.7-kb deletional alpha-thalassemia in Thai patients. 1218 10

A large number of mutations have been described in the human beta-globin locus causing thalassemia or various hemoglobinopathies. However, only a very limited number of these mutations have been studied in animal model systems in the context of the human beta-globin locus. We report here the use of the GET Recombination system with an EcoRI/Kan(R) counterselection cassette to facilitate the introduction of the HbE (codon 26, GAG-->AAG mutation and the codon 41-42 (-TTCT) deletion, two mutations found in high frequency in South-East Asia, into the human beta-globin locus. The counterselection cassette was first inserted into the target sequence in the beta-globin gene, and then a PCR fragment carrying the required modification was used to replace it. Efficient counterselection depends upon the tight regulation of the highly toxic EcoRI endonuclease gene by expression of lacI(q). Induction by IPTG during counterselection efficiently eliminates non-recombinant bacterial clones. The technique can be performed on any known gene sequence using current BAC technology, allowing identification and comparative functional analysis of key regulatory elements, and the development of accurate animal models for human genetic disorders.
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PMID:Insertion of common mutations into the human beta-globin locus using GET Recombination and an EcoRI endonuclease counterselection cassette. 1252 64

Thalassemia is a common inherited disease in the Mediterranean region. We here report a mutation new to the Lebanese population: the insertion of a G nucleotide at codons 8/9 [(+G) AAG-TCT (Lys-Ser) --> AAG-G-TCT (beta0)] of the beta-globin gene in a thalassemic patient with a mild phenotype. We discuss the possible factors that play a role in alleviating the severity of the disease in this case.
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PMID:The codons 8/9 (+G) mutation found for the first time in the Lebanese population. 1260 87

Hemoglobin (Hb) Hekinan (alpha27; Glu-Asp) is a rare alpha-chain variant found mainly in Japanese and Chinese whereas Hb E (beta26; Glu-Lys) is common among Southeast Asians. We report a hitherto undescribed condition in which these two variants co-segregate. The proband was a 25-yr-old Thai woman who was encountered with the presence of mild hypochromic microcytosis with Hb 8.2 g/dL, hematocrit (Hct) 26.0%, Mean Corpuscular Value (MCV) 68.6 fL, Mean Corpuscular Hemoglobin (MCH) 21.6 pg and Mean Corpuscular Hemoglobin Concentration (MCHC) 31.5 g/dL. Although Hb electrophoresis at alkaline pH did not show any abnormal band except Hb E in addition to Hb A, high performance liquid chromatography analysis revealed abnormal peaks at the Hb A and Hb E positions. DNA analysis of the proband revealed a GAG-GAT mutation at codon 27 of the minor alpha1-globin gene for Hb Hekinan in trans to the South-east Asian (SEA) deletional alpha-thalassemia 1 determinant and a GAG-AAG mutation at codon 26 of the beta-globin gene for Hb E. She was therefore a triple heterozygote for these three anomalies. Family study identified that her mother was a double heterozygote for Hb Hekinan and Hb E without alpha-thalassemia whereas her father was a classical Hb H disease patient. The genotype-phenotype relationship observed in this Thai family with complex hemoglobinopathies is presented and a simple DNA assay based on the polymerase chain reaction methodology for rapid diagnosis of Hb Hekinan is described.
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PMID:Complex interaction of Hb Hekinan [alpha27(B8) Glu-Asp] and Hb E [beta26(B8) Glu-Lys] with a deletional alpha-thalassemia 1 in a Thai family. 1269 66


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