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

We describe the hematological and DNA characterization of Hb D-Punjab [beta121(GH4)Glu-->Gln] in Thailand. Nine patients from five unrelated families were studied; four patients were simple carriers of Hb D-Punjab, two were compound heterozygotes for Hb D-Punjab/beta+-thalassemia; another two patients were double heterozygotes for Hb D-Punjab and alpha-thalassemia-2, and one patient was a compound heterozygote for Hb D-Punjab and Hb E [beta26(B8)Glu-->Lys]. Typical thalassemic indices with hypochromic microcytosis were observed in compound Hb D-Punjab/ beta+-thalassemia and Hb D-Punjab/Hb E but normal hematological profiles were observed in the remaining cases. DNA sequencing of the beta-globin gene identified the GAA-->CAA substitution at codon 121 causing Hb D-Punjab in all cases, and the -28 (A-->G) mutation for the beta+-thalassemia alleles. beta-Globin gene haplotype analysis demonstrated, for the first time, that all these Asian beta(D-Punjab) globin genes were associated with haplotype [-++-+++], previously undescribed in other populations. The finding of Hb D-Punjab in Thailand is compatible either with an independent origin of this abnormal hemoglobin or a spread of the Hb D-Punjab gene with a single origin among Asians.
 ...
PMID:Molecular characterization of Hb D-Punjab [beta121(GH4)Glu-->Gln] in Thailand. 1240 91

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.
 ...
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.
 ...
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

ATRX is a centromeric heterochromatin binding protein belonging to the SNF2 family of helicase/ATPases with chromatin remodeling activity. Mutations in the human ATRX gene result in X-linked alpha-thalassaemia with mental retardation (ATRX) syndrome and correlate with changes in methylation of repetitive DNA sequences. We show here that ATRX also functions to regulate key stages of meiosis in mouse oocytes. At the germinal vesicle (GV) stage, ATRX was found associated with the perinucleolar heterochromatin rim in transcriptionally quiescent oocytes. Phosphorylation of ATRX during meiotic maturation is dependent upon calcium calmodulin kinase (CamKII) activity. Meiotic resumption also coincides with deacetylation of histone H4 at lysine 5 (H4K5 Ac) while ATRX and histone H3 methylated on lysine 9 (H3K9) remained bound to the centromeres and interstitial regions of condensing chromosomes, respectively. Inhibition of histone deacetylases (HDACs) with trichostatin A (TSA) disrupted ATRX binding to the centromeres of hyperacetylated chromosomes resulting in abnormal chromosome alignments at metaphase II (MII). Similarly, while selective ablation of ATRX by antibody microinjection and RNA interference (RNAi) had no effect on the progression of meiosis, it had severe consequences for the alignment of chromosomes on the metaphase II spindle. These results suggest that genome-wide epigenetic modifications such as global histone deacetylation are essential for the binding of ATRX to centromeric heterochromatin. Moreover, centromeric ATRX is required for correct chromosome alignment and organization of a bipolar meiotic metaphase II spindle.
 ...
PMID:ATRX, a member of the SNF2 family of helicase/ATPases, is required for chromosome alignment and meiotic spindle organization in metaphase II stage mouse oocytes. 1524 86

Hb E [beta26(B8)Glu-->Lys], is the most common abnormal hemoglobin (Hb) in Southeast Asian populations. The hitherto highest frequencies of the Hb E gene (HBB*E) in large population samples, approximately 0.3, were observed in the southern part of northeastern Thailand. The finding of even higher frequencies in a small, isolated Austroasiatic group in Northeast Thailand prompted us to examine samples of three Austroasiatic populations in southern Laos (official designation: Lao Theung), an area inhabited by numerous ethnic groups belonging to the Mon-Khmer branch. Blood samples were collected from a total of 603 adult subjects. The HBB*E frequencies were 0.426 in the So of Khammuan Province, 0.433 in the Alak/Ngeh of Sekong Province and 0.253 in the Oy of Attapeu Province. The HBB*E frequencies in the So and Alak/Ngeh are the highest observed in Southeast Asia in representative population samples. None of the common Southeast Asian beta-thalassemia (thal) mutations were found. The results are discussed with respect to natural selection by malaria, selection time, effects of beta-thal and the ethnic history of the population of Southeast Asia.
 ...
PMID:The 'hot-spot' of Hb E [beta26(B8)Glu-->Lys] in Southeast Asia: beta-globin anomalies in the Lao Theung population of southern Laos. 1548 86

Hemoglobin E (HbE, beta26 Glu-->Lys) is the most common abnormal Hb variant in the world, and found in greatest frequency in Southeast (SE) Asia. In the United States, HbE is the third most prevalent variant (after HbS and HbC); and its now increasing frequency is due to immigration from SE Asia. HbE homozygotes present a benign clinical picture, but when HbE is coupled with beta0-thalassemia or HbS, variably severe hemoglobinopathies arise. To date, there are no transgenic animal models of HbE-related diseases. We report here the creation of transgenic mice expressing human HbE as a step toward creating animal models for HbE-related diseases. The betaE mice exhibit red blood cell hypochromia and target cells consistent with those observed in human patients exhibiting HbE trait. Furthermore, the transgenic HbE hemolysates contain increased amounts of Hb oxidation products.
 ...
PMID:Generation of transgenic mice expressing human hemoglobin E. 1552 49

Christmas Island is a remote Australian territory 2,400 km north of Perth. Health care is administered from Perth. The population is predominantly Chinese, with some Malay, Indian and European. As hemoglobinopathies are known to be common amongst these ethnic groups, a study was performed to determine their prevalence and significance in the Christmas Island population. Three-hundred and sixty-four individuals (adults and children) were tested. All subjects were assessed by full blood count, alpha-globin multiplex polymerase chain reaction (PCR) and PCR testing for Hb Constant Spring [alpha142, Term-->Gln, TAA-->CAA (alpha2)]. Microcytic patients (MCV <80 fL) were further investigated by high performance liquid chromatography (HPLC) and serum ferritin was determined. Where present, beta-thalassemia (thal) mutations were characterised by PCR. Thirty-four subjects (9.3%) were microcytic and of these five were iron deficient. The remainder were heterozygous for a hemoglobinopathy, giving a 9.1% incidence of hemoglobinopathies in Christmas Islanders. alpha-Thalassemia was identified in 23 subjects, seven of whom were heterozygous for alpha(-3.7); the remaining 16 were heterozygous for the - -SEA deletion. One case of heterozygous deltabeta-thal and one case of heterozygous Hb E [beta26(B8)Glu-->Lys] was detected. Of the eight subjects heterozygous for beta-thal, at least five mutations are represented, indicating a diverse and heterogeneous origin for this population.
 ...
PMID:Hemoglobinopathies in the Christmas Island population. 1565 94

A T-->C mutation in the beta-globin gene at codon 110 that produces the hyper unstable variant Hb Showa-Yakushiji was identified in four unrelated individuals in India. It was found in a compound heterozygous state with other mutations producing beta-thalassemia (thal) or Hb E [beta26(B8)Glu-->Lys]. The mutation producing this abnormal hemoglobin (Hb) was found on the same haplotype in all these patients but differed from the Japanese haplotype, indicating its independent origin in India.
 ...
PMID:Hb Showa-Yakushiji [beta110(G12)Leu-->Pro] in four unrelated patients from west Bengal. 1576 52

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.
 ...
PMID: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. 1576 59

Hemoglobin (Hb) C (alpha2beta(2)6Glu-Lys) is a variant Hb found mainly in West Africa where individuals carrying both Hb C and Hb S (alpha2beta(2)6Glu-Val) usually have a disease similar to sickle cell disease. The Hb C molecule has reduced solubility leading to crystal formation and hemolytic anemia. We report a hitherto undescribed interaction of Hb C and Hb Malay (alpha2beta(2)19Asn-Ser) in a Thai individual. She was a 24-year-old pregnant woman with moderate anemia who had the following hematologic data; Hb 8.9 g/dl, Hct 30.0%, MCV 81.0 fl, MCH 24.1 pg, MCHC 29.7 g/dl, RDW 17.1% and instead of Hb crystal a marked number of target cell in peripheral blood was observed. Hb analysis revealed 22.5% Hb Malay, 64.6% Hb C and 4.5% Hb A2. Globin gene analyses demonstrated that she carried the betaC mutation (beta6: GAG-AAG) in trans to the betaMalay mutation (beta19: AAC-AGC). Hematologic data of the patient were compared to those of the compound heterozygote for Hb C and Hb E (alpha2beta(2)26Glu-Lys) found in 5 other unrelated Thai pregnant women and 11 pregnant women with Hb C heterozygote with or without co-inheritance of alpha-thalassemia who had much lower Hb C levels and the non-pregnant women with Hb C heterozygote and a compound Hb E/Hb Malay syndrome. Different genotype-phenotype correlations observed in these Thai patients with Hb C disorders are illustrated.
 ...
PMID:Compound heterozygote states for Hb C/Hb Malay and Hb C/Hb E in pregnancy: a molecular and hematological analysis. 1598 9


<< Previous 1 2 3 4 5 6 7 8 9 Next >>