Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sickle-cell anemia results from an A leads to T transversion in the second nucleotide of codon 6 of the beta-globin gene. We now report an uncommon beta-thalassemia gene that contains a deletion of this nucleotide. Thus, one mutation (GAG leads to GTG) produces sickle-cell anemia, while the other (GAG leads to GG) eliminates beta-globin production. These data establish that different alterations affecting one specific nucleotide can produce either an abnormal hemoglobin or beta-thalassemia. Moreover, the nucleotide sequence comprising codons 6-8 of the beta-globin gene appears to be particularly susceptible to mutations affecting nucleotide number.
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PMID:beta-Thalassemia due to a deletion of the nucleotide which is substituted in the beta S-globin gene. 631 Sep 91

A new T --> A base substitution, identified inside the 5' regulatory region of the human Agamma globin gene (Agamma-499 T -->A), is reported. This nucleotide change was found to be linked in cis with the mutation producing sickle cell anemia (CD6 GAG-->GTG: betaS gene).
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PMID:A new base substitution in the 5' regulatory region of the human Agamma globin gene is linked with the betaS gene. 878 81

Sickle hemoglobin (Hb S; beta Glu6Val) is due to an A<T transversion in codon 6 of the beta-globin gene. Several Hb S variants have both the Hb S mutation plus another mutation in the same beta-globin gene. Some of these variant hemoglobins can lead to sickle cell disease even in the simple heterozygote. Moreover, some variant hemoglobins mimic Hb A, S, or C on one or several clinical laboratory diagnostic tools, thus making their correct identification potentially problematic. The authors report a novel Hb S variant hemoglobin, Hb S-South End (beta Glu6Val, GAG>GTG; beta Lys132Asn, AAA>AAC). When present alone, the beta Lys132Asn mutation has low oxygen affinity. Therefore, this mutation may enhance the polymerization of the Hb S variant. Furthermore, the variant hemoglobin mimics Hb A on high-pressure liquid chromatography, and its identity is not easily diagnosed. A succinct review of variant sickle hemoglobins is also presented.
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PMID:A novel sickle hemoglobin: hemoglobin S-south end. 1554 18

The determination of the prevalence of inherited hemoglobin (Hb) disorders in endemic areas is important in order to develop programs for their control and management. The aim of this study is to determine the prevalence of inherited Hb diseases in Guinea-Bissau which is situated on the west coast of Africa, between Senegal and Guinea. One thousand and fifty-seven blood samples were collected and analyzed with high performance liquid chromatography (HPLC) for detection of beta-thalassemia (thal) and Hb variants, and by gap polymerase chain reaction (gap-PCR) for the detection of deletions in the alpha-globin genes. We found 4.7% children were heterozygous for Hb S [beta6(A3)Glu-->Val, GAG -->GTG], 0.2% were homozygous for Hb S, and 0.3% were heterozygous for Hb C [beta6(A3)Glu-->Lys, GAG -->AAG]. One child had heterozygous beta+-thal, 13.8% were heterozygous for the -alpha3.7 deletion, 1.5% were homozygous for the -alpha3.7 deletion, and 1.5% were heterozygous for the -alpha4.2 deletion. We recommend national screening programs to focus primarily on sickle cell disease, since beta-thal is rare, and the observed alpha-thal deletions are of minor genetic importance.
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PMID:Inherited hemoglobin disorders in Guinea-Bissau, West Africa: a population study. 1684 Feb 26

A 38-year-old Ghanaian man presented with a 6-month history of worsening pruritus, jaundice, and ascites. He was previously fit and well and rarely drank alcohol. Screening tests for chronic liver disease including viral, autoimmune, and other metabolic causes including iron overload were unremarkable. A liver biopsy performed at the referring hospital demonstrated intralobular cholestasis and cirrhosis. He was listed for liver transplantation but subsequently developed sepsis with multiple organ failure and died. The sickle solubility test was positive. Blood smear showed cells consistent with liver failure and no sickle cells. Hemoglobin electrophoresis revealed HbA2 2.8%, HbF 0.5%, and HbS greater than HbA (49.6% vs. 41.3%) in the absence of blood transfusion. Sequence analysis of the beta-globin genes showed he was a compound heterozygote for the Hbs mutation at codon 6 (CAG --> GTG) and a novel mutation at position 844 of intron 2 (betaIVS2-844 C --> A). A diagnosis of sickle hepatopathy causing decompensated cirrhosis was made. This case is unusual insomuch as this patient was asymptomatic for over 35 years and represents a novel presentation of sickle cell disease. Sickle cell disease should be considered in appropriate patients when unusual presentations of liver disease arise.
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PMID:Sickle liver disease--an unusual presentation in a compound heterozygote for HbS and a novel beta-thalassemia mutation. 1756 24

Hemoglobinopathies are the most common genetic diseases in Turkey. The incidence of sickle cell trait is 10.0% and beta-thalassemia (beta-thal) trait is 3.7% in the Cukurova region of southern Turkey. Sickle cell anemia is prevalent in the Cukurova region, but beta-thal is seen all over the country. A prenatal diagnosis center was established in 1992 at Adana, Turkey, for the prevention of sickle cell anemia and beta-thal. Fifteen hundred and seventy-five fetuses were examined at the Cukurova University Hospital, Adana, Turkey. Three hundred and eighty-six fetuses were diagnosed as homozygous or compound heterozygous for sickle cell anemia and beta-thal. A total of 15 different beta-thal mutations were characterized in the parents. The incidence of the IVS-I-110 (G > A) mutation accounted for about 50.0% of the parents with beta-thal trait. Twenty-four different genotypes were observed in this study. A total of 286 fetuses were diagnosed with homozygous sickle cell disease, 57 fetuses were beta-thal homozygotes, 25 fetuses were compound heterozygotes with Hb S [beta6(A3)Glu-->Val, GAG > GTG], and 18 of the fetuses were double heterozygotes for beta-thal mutations.
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PMID:Prenatal diagnosis of sickle cell anemia and beta-thalassemia in southern Turkey. 1906 29

Sickle cell anemia is one of the most common autosomal recessive diseases in the world. Patients with sickle cell anemia have variable penetrance and it is hard to predict the risk and timing of complications. It is characterized by a point mutation in the beta-globin gene (GAG --> GTG) and the production of hemoglobin S. The latter leads to decreased deformability of the red blood cells (RBCs) that adhere to endothelia cells culminating in vascular occlusion and its sequelae of tissue ischemia and organ damage. Moreover, sickled RBCs undergo intravascular hemolysis and accelerated erythropoesis. The hallmarks of this disease are shortened RBC survival and vaso-occlusive crises. For the past ten years, the pathophysiology of this disease has been better elucidated and has led to significant improvements in the standard of care. Vaso-occlusion is now understood to be a complex event that involves abnormal interactions between RBCs, leukocytes, endothelial cells and the coagulation pathways. The field of translational research in sickle cell anemia has expanded greatly and has led to new clinical trials with new therapeutic agents and strategies. In this paper, we review the drugs that are now being investigated in the treatment of sickle cell anemia.
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PMID:Investigational drugs in sickle cell anemia. 1978 Jul 9

Hb D-Punjab [beta121(GH4)Glu-->Gln, GAA>CAA], common in the northern Indian province, is often unexpectedly found in other populations. To study the multi centric origin of this variant which is causing sickle cell disease in association with Hb S [beta6(A3)Glu-->Val, GAG>GTG], we have examined the haplotype of the Hb D allele in different populations. We studied 43 alleles from south Iran (Hormozgan and Fars provinces) and 14 from Holland and Belgium using high performance liquid chromatography (HPLC), capillary electrophoresis, direct sequencing and/or restriction enzyme analysis. In Iranians, four haplotypes were observed at different frequencies: haplotype I [+ - - - -,+ +] at 67.5%, subhaplotype I' [+ - - - -,- +] at 17.5%, haplotype V [- + - - +,+ +] at 10.0% and haplotype III [- + - + +,+ +] at 5.0%. All European cases were on haplotype I. The occurrence of high Hb D frequencies on a single haplotype in specific regions can be expected if we consider founder effect and genetic drift mechanisms. However, considering that haplotype I is the most common haplotype worldwide, that Hb D-Punjab is reported in different populations on different haplotypes, and that codon beta121 is a site on which six different mutations are reported, we may expect to observe Hb D-Punjab in different populations, possibly because of a relatively higher occurrence of de novo mutations, generating unexpected risk from mixtures of allochtonous Hb S and indigenous Hb D-Punjab or vice versa.
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PMID:Multi centric origin of Hb D-Punjab [beta121(GH4)Glu-->Gln, GAA>CAA]. 2035 59

beta-Thalassemia (beta-thal), is caused by reduced or absent synthesis of beta-globin chains resulting in impaired erythropoiesis. It is the most common single gene defect disease in Greece, with heterozygous rates reaching, on average, 8% in the general population. Here, we performed molecular analyses on 199 unrelated beta-thal and compound beta-thal/sickle cell disease patients, of whom 157 originated from three prefectures of South-Western Greece, namely Achaia, Ilia and Etoloakarnania. Our results indicate that the frequency of specific HBB gene mutations, namely the HBB:c.118C>T (codon 39, C>T), HBB:c.92+6T>C (IVS-I-6, T>C), and HBB:c.20A>T [Hb S, beta6(A3)Glu-->Val, GAG>GTG], present distinct distribution patterns in the Achaia and Ilia prefectures (p < 0.001, p < 0.003 and p < 0.002, respectively). This detailed analysis of the distribution of the HBB gene mutations is useful for genetic counseling in the region, and illustrates that the identification of the HBB gene mutation spectrum in this region is necessary for population carrier screening and for efficient provision of prenatal diagnosis.
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PMID:Region-specific genetic heterogeneity of HBB mutation distribution in South-Western Greece. 2064 31

Sickle cell disease (SCD) is an inherited red cell disorder, characterized by the tendency of haemoglobin S or sickle haemoglobin to polymerize and assume a characteristic sickle shape. Molecular analysis has been the mainstay of detection method when confirmation is required. Previously a polymerase chain reaction (PCR)-based restriction enzyme analysis was used for this purpose. A simple bidirectional allele-specific amplification, recently described by Waterfall in 2001 was used to detect the GAG --> GTG mutation on codon 6 of the beta globin gene. Two sets of primers for the mutant and the wild type alleles were used in a single PCR reaction to amplify the regions of interest. The resultant PCR products will produce two fragments at 517 and 267 base pair (bp) respectively. This report highlights the investigations for SCD in the family of a 16-year old girl with recurrent painful crisis affecting the lower limbs whereby the family members are asymptomatic for the disease. Her haemoglobin electrophoresis at an alkaline pH showed dense bands at the HbS and HbF regions, while her father and two sisters had bands at HbS, HbF and HbA. The PCR analysis showed that she was homozygous for the mutation by the presence of only one band at 267 bp fragment, while the father and her sisters were heterozygotes, with the presence of two bands at 267 as well as 517 bp fragments. DNA sequencing of the sample confirmed the mutation. In conclusion, this case report highlighted the simple and cheap yet practical method for molecular confirmation of the presence of HbS gene in subjects with homozygous or heterozygous state of the condition.
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PMID:A family study of HbS in a Malay family by molecular analysis. 2132 86


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