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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We developed a rapid and simple method to diagnose the molecular defects of beta-thalassemia in Chinese patients. This method involves the selective amplification of a DNA fragment from human beta globin gene with specific oligonucleotide primers, followed by digestion with restriction enzymes that recognize artificially created or naturally occurring restriction sites. To detect the 4-nucleotide deletion of codon 41-42, we introduced a single mismatch nucleotide into the 3' end of the upstream primer to create an artificial Taq I restriction site. With a similar approach, an artificial Rsa I site was generated to detect the nucleotide 654 mutation (C-->T) of IVS-2, and Alu I restriction site was created to detect the codon 17 mutation (A-->T), and EcoRI restriction site was created for the -28 mutation (A-->G), a Rsa I restriction site was created for the nucleotide 5 mutation (G-->C) of IVS-1, and a Spe I restriction site was created to distinguish the codon 71 (+T) and codon 71/72 (+A) mutations from a normal sequence. The other eight rare mutations that occur in the genes of the Chinese people naturally create or abolish restriction sites. Using this kind of approach, we are able to provide a simple, rapid, accurate, and nonradioactive method to detect the genetic defects of beta-thalassemia in the Chinese population. It should be used not only for routine screening but also for prenatal diagnosis.
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PMID:Rapid diagnosis of beta-thalassemia mutations in Chinese by naturally and amplified created restriction sites. 139 61

A novel technique names 3' Base-Specific-PCR was used to detect the gene mutations of beta-thalassemia directly without ASO(Allele-specific Oligonucleotide) dot hybridization. Four oligonucleotide primers with 3' Base-Specificity was designed and synthesized according to 3 most common mutations in beta globin gene among Chinese (codon 41-42-(-TTCT) frameshift, codon 17 (A-T) and IVS-II-654(C-T) point mutation). Two fetuses at high risk for beta-thalassemia were diagnosed in early pregnancy by using the 3'-Base-Specific PCR technique. The results were confirmed by means of PCR combined with ASO techniques.
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PMID:[3' base-specific-PCR technique and its application to prenatal diagnosis of beta-thalassemia]. 165 Jun 33

Haematological, clinical and some molecular genetic features of homozygous sickle cell (SS) disease in Saudi Arabia have been compared in 33 patients from the Eastern Province (Eastern) and 30 from the South Western Province (Western). Eastern patients all had the Asian beta globin haplotype whereas Western patients were more variable but predominantly of the Benin haplotype. Eastern patients had more deletional alpha thalassaemia, higher total haemoglobin and fetal haemoglobin levels, and lower HbA2, mean cell volume, reticulocytes, and platelet counts. Clinically, Eastern patients had a greater persistence of splenomegaly, a more normal body build and greater subscapular skin fold thickness, and Western patients had more dactylitis and acute chest syndrome. Painful crises and avascular necrosis of the femoral head were common and occurred equally in both groups. The disease in the Eastern province has many mild features consistent with the higher HbF levels and more frequent alpha thalassaemia but bone pathology (painful crises, avascular necrosis of the femoral head, osteomyelitis) remains common. The disease in the West is more severe consistent with the Benin haplotype suggesting an African origin.
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PMID:Two different forms of homozygous sickle cell disease occur in Saudi Arabia. 171 63

An etiological examination was performed on the DNA of a 13-year-old Zairean girl, who had some abnormalities in hematological and red cell morphological examinations and was homozygote for an abnormal Hb like HbS. DNA was amplified by the PCR method to obtain 1.7 kb size DNA containing the 5' region of the beta globin gene. The amplified DNA was digested with Eco 81 I and electrophoresis of the digest revealed the absence of its active site, which is on codons beta 5-7 (CCTGAGGAG) of the normal DNA. Sequencing of the cloned DNA by the dideoxy method confirmed that the codon beta 6 (GAG, Glu) mutated to a new codon GTG (Val) which is the beta S globin gene producing abnormal HbS. The haplotype of the chromosome having beta S gene was --+---++, which is the most common type in Zaire area. On the other hand, when the genomic DNA was digested with Bgl II or Bam HI and hybridized to an alpha probe, a fragment (16 kb/Bgl II or 10.5 kb/Bam HI) in addition to the normal ones (12.5 and 7.5 kb/Bgl II or 14 kb/Bam HI) was observed. This resulted from the deletion of 3.7 kb from the alpha gene arrangement, which led to alpha-thalassemia-2 (genotype: alpha 3.7-/alpha alpha). A family study demonstrated that her parents were heterozygote for HbS and her father had alpha-thalassemia-2.
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PMID:[Molecular analysis of an African family with sickle cell disease and alpha-thalassemia-2]. 177 70

1. The molecular abnormality of a patient with thalassemia intermedia was identified by DNA amplification (PCR) combined with the use of synthetic oligonucleotide probes. 2. The patient is a homozygote for the T----C substitution at position 6 of the first intervening sequence (IVS1-6) of the beta globin gene. 3. On the basis of this finding, the family, which had been previously reported by us to be a carrier of an unusually mild beta-thalassemia gene, was actually the first example reported of the clinical and biochemical features of beta-thalassemia-Portuguese type.
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PMID:Beta-thalassemia intermedia and IVS-1 NT6 homozygosis in Brazil. 182 28

A mild, non-transfusion dependent, beta thalassaemia phenotype is described in a Dutch patient homozygous for a mutation in the cleavage-polyadenylation sequence of the beta globin gene. The molecular basis of the mutation, AATAAA greater than AATGAA, was determined using denaturing gradient gel electrophoresis (DGGE) and direct sequencing of genomic DNA amplified by the polymerase chain reaction (PCR). Different fragments of the beta globin gene were amplified and analysed on DGGE for the presence of mutations. The fragment with an abnormal melting behaviour was reamplified and the base substitution in the polyadenylation sequence was identified by direct sequencing.
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PMID:Homozygous beta+ thalassaemia owing to a mutation in the cleavage-polyadenylation sequence of the human beta globin gene. 185 30

The clinical, haematological, and some molecular genetic features of 17 Orissan Indian patients with sickle cell-beta+ thalassaemia (S beta+ thal) are described and compared with those in 131 Indian patients with homozygous sickle cell (SS) disease. Patients with S beta+ thal had higher Hb A2 levels, and lower mean cell volume (MCV) and mean cell haemoglobin (MCH) compared to SS disease but no other haematological difference of statistical significance. High levels of Hb F occurred in both genotypes and the alpha+ thalassaemia gene frequency reached 0.47 in S beta+ thal and 0.32 in SS disease. Clinically there were no significant differences between the genotypes indicating that the low levels of HbA (3-5%) in this condition were insufficient to modify the clinical features. The thalassaemic beta globin gene is inactivated by a G----C mutation at position 5 of the first intron of the beta globin gene (IVS1-5 G----C) in all cases. This finding should facilitate the introduction of a prenatal diagnosis programme aimed at the prevention of beta thalassaemia or S beta+ thalassaemia in that population.
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PMID:Sickle cell-beta+ thalassaemia in Orissa State, India. 200 23

During a 10-month period, 10 couples originating from Africa (3), the tropics (1) and the thalassemia-belt region (6), living in Switzerland, requested prenatal diagnosis of hemoglobinopathies. Hb SS (twice), Hb Bart's (Hydrops fetalis) and beta-thalassemia major were diagnosed either by gene mapping or by direct detection of the mutations in DNA amplified by the PCR procedure. Whenever it was possible to obtain fetal blood or tissue, diagnosis was confirmed. In one Vietnamese man, concomitant existence of alpha-thal 1 with beta-thalassemia resulted in an unusually high Hb level because of balanced alpha and beta globin synthesis. The 10 couples examined originated from 7 different countries and presented at least 7 different Hb pathologies. This variety of pathologies represents the main difficulty for prenatal diagnosis of hemoglobinopathies in a non-endemic country. A diagnostic approach to overcome this problem is developed.
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PMID:Prenatal diagnosis of thalassemia and hemoglobinopathies in Switzerland. 200 49

In addition to local sequence elements the regulation of the high-level, development- and tissue-specific expression of the human beta globin gene cluster appears to require distant regulatory sequences which have been termed locus control region. In the chromatin of erythroid cells the locus control region is characterized by four DNaseI hypersensitive sites that are located 6-18 kb 5' of the epsilon globin gene. The definition of the sequences minimally required for locus control region activity is likely to further the understanding of its physiology and will be of interest for the development of somatic gene therapy strategies of the hemoglobinopathies. We present here the analysis of a family with a 3,030-bp deletion of sequences upstream of the epsilon globin gene including the most 3' locus control region element and cosegregating beta(0) thalassemia. The deletion is linked in cis to a structurally and functionally normal beta globin gene. The proximal element of the locus control region does not therefore appear to be necessary for beta globin gene activity in vivo.
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PMID:The proximal element of the beta globin locus control region is not functionally required in vivo. 204 Jun 96

The DNA deletion associated with an example of (epsilon gamma delta beta)zero thalassemia (Scottish-Irish type) was characterized. The deletion is approximately 205 kb in length and involves the epsilon, G gamma, A gamma, delta, and beta globin genes. The breakpoint is located 263 bp 3' to exon 3 of the beta globin gene. An LI (KpnI) repeat element approximately 320 bp in size is found at the 3' end of the novel DNA sequence. Different clinical phenotypes for three heterozygous neonates suggest that the deletion alone does not predict severity of (epsilon gamma delta beta)zero thalassemia at this age.
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PMID:Molecular and hematologic characterization of Scottish-Irish type (epsilon gamma delta beta)zero thalassemia. 224 32


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