1/52. Laboratory recognition of a rare hemoglobinopathy: hemoglobins SS and SG(philadelphia) associated with alpha-thalassemia-2.This article describes the laboratory investigation of an unusual hemoglobinopathy involving hemoglobin (Hb) S, HbSG(philadelphia), and alpha-thalassemia-2 in a patient whose phenotype was HbSC by alkaline electrophoresis. Findings of a mean corpuscular volume of 62 fL and microcytes on the blood smear were inconsistent with HbSC disease. The patient's clinical course over several years had been mildly symptomatic. Testing in our hospital laboratory using isoelectric focusing and cation-exchange high-performance liquid chromatography to separate hemoglobins showed an unknown variant. Additional studies, including globin chain electrophoresis, reverse-phase high-performance liquid chromatography, and polymerase chain reaction-based dna analysis were performed at reference laboratories, which reported the following findings: HbG(philadelphia) associated with alpha-thalassemia-2, HbS and HbG(philadelphia), and the alpha-globin deletions defining the -alpha3.7/-alpha3.7 genotype. The hemoglobin molecular defects, alpha-thalassemia-2, and the pattern of inheritance are discussed.- - - - - - - - - - ranking = 1keywords = sea (Clic here for more details about this article) |
2/52. Hb Aghia Sophia [alpha62(E11)Val-->0 (alpha1)], an "in-frame" deletion causing alpha-thalassemia.In this report we describe a case of Hb H disease due to the interaction of the --(MED 1) deletion with a new alpha( )-thalassemia determinant. The molecular analysis of the proband's genomic dna was carried out by polymerase chain reaction amplification and sequencing of both alpha genes of the alpha( )-thalassemia chromosome and revealed a deletion of codon 62 of the alpha1 gene. This dna triplet codes for a valine residue at the E11 alpha helix, which is located in the interior of the heme pocket. Substitutions of valine E11 with other amino acid residues in the alpha as well as beta polypeptide chains lead, in the heterozygous carrier, either to Hb M disease or to congenital non-spherocytic hemolytic anemia. We assume that the deletion of valine at alpha62(E11) disrupts the conformation of the alpha chain to such an extent that the mutated subunit is rapidly removed by proteolysis. The final result is an alpha-thalassemia phenotype rather than an unstable hemoglobin syndrome. This conclusion is supported by the apparent absence of an abnormal alpha chain in the peripheral blood of the patient.- - - - - - - - - - ranking = 2keywords = sea (Clic here for more details about this article) |
3/52. Hb Sallanches [alpha104(G11)Cys-->Tyr]: a rare alpha2-globin chain variant found in the homozygous state in three members of a Pakistani family.We have identified a rare alpha2-globin chain variant, Hb Sallanches [alpha104(G11) Cys-->Tyr], in a Pakistani family having three homozygous patients with transfusion-dependent Hb H disease. This variant, previously reported in a French patient and a West Indian homozygous patient with Hb H disease, is due to a mutation at codon 104 (TGC-->TAC). This is the third case of Hb Sallanches and the first case with three homozygous patients reported in pakistan. Due to the different ethnic origins of the patients, it is very likely an independent mutation.- - - - - - - - - - ranking = 2keywords = sea (Clic here for more details about this article) |
4/52. diagnosis of concurrent hemoglobin h disease and heterozygous beta-thalassemia.Definitive diagnosis of concurrent hemoglobin (Hb) H disease and heterozygous beta-thalassemia cannot be made from Hb analysis alone, but necessitates genotype analysis and family study. Interactions between alpha- and beta-thalassemia must be considered when investigating moderate to severe hypochromic microcytic anemia of uncertain cause in adult patients from areas with a high prevalence of globin gene mutations.- - - - - - - - - - ranking = 5keywords = sea (Clic here for more details about this article) |
5/52. Atypical hemoglobin h disease in a Thai patient resulting from a combination of alpha-thalassemia 1 and hemoglobin Constant Spring with hemoglobin j Bangkok heterozygosity.A case of hemoglobin h disease in combination with hemoglobin Constant Spring and a beta-globin chain variant is reported in a 3-yr-old Thai girl. On routine cellulose acetate electrophoresis, one abnormal band in addition to the hemoglobins A, A2, H, Bart's and Constant Spring was detected. The amount of this abnormal band movement towards more anodic to the hemoglobin a was 35.7%. dna analysis of the alpha-globin gene cluster by polymerase chain reaction (PCR) revealed a combination of defects caused by the SEA-type alpha-thalassemia 1 and the alpha-Constant Spring gene. Analysis of beta-globin gene by PCR and dna sequencing also detected the heterozygosity for the GGC-GAC mutation at codon 56, leading to a substitution of aspartic acid for glycine resulting in the hemoglobin j Bangkok. The hematologic data of this unusual case of hemoglobin h disease are presented and compared with two compound heterozygotes for hemoglobin j Bangkok and alpha-thalassemia 1 found in the patient's father and grandfather. A simple dna assay based on an allele-specific PCR for rapid diagnosis of the hemoglobin j Bangkok is also described.- - - - - - - - - - ranking = 6keywords = sea (Clic here for more details about this article) |
6/52. Acute myeloid leukemia precipitated by dengue virus infection in a patient with hemoglobin h disease.We report a unique case of refractory acute myeloid leukemia (AML) precipitated by dengue virus induced marrow aplasia in a Chinese patient with hemoglobin (Hb) H disease. The quick temporal sequence of the three marrow abnormalities: hereditary hemoglobinopathy, reactive viral induced marrow change and malignant neoplastic process is highly unusual. Neither HbH disease nor viral induced marrow aplasia has known associations with AML. We propose that this unique case of AML may be caused by cytokine hyperstimulation in a stressed marrow.- - - - - - - - - - ranking = 6keywords = sea (Clic here for more details about this article) |
7/52. A novel splice acceptor site mutation of the alpha2-globin gene causing alpha-thalassemia.A novel nondeletional alpha-thalassemia mutation that affects rna processing, changing the alpha2 IVS-II-142 splice acceptor consensus sequence from AG to AA, has been detected in an Argentinian patient with Hb H disease and her daughter.- - - - - - - - - - ranking = 1keywords = sea (Clic here for more details about this article) |
8/52. Haemoglobin H disease due to (--SEA) alpha-globin gene deletion and alpha2-codon 30 (DeltaGAG) mutation: a family study.A Chinese family in which two siblings suffer from haemogloblin (Hb) H disease due to (--SEA) alpha-globin gene deletion and alpha2-codon 30 (DeltaGAG) mutation is described. Both siblings are transfusion-independent and have survived to adulthood. In contrast to previous report of hydrops fetalis associated with zeta-alpha-thal-1 and alpha2-codon 30 (DeltaGAG) mutation, the zeta-globin genes are intact in the two siblings, which most probably alleviates the gamma-chain excess and protects the fetus from severe anaemia. Correlation of genotype with phenotype in Hb H disease is important for genetic counselling, especially in the antenatal setting.- - - - - - - - - - ranking = 6keywords = sea (Clic here for more details about this article) |
9/52. Hb H hydrops foetalis syndrome: a case report and review of literature.Haemoglobin H (Hb H) disease is caused by deletion or inactivation of three alpha-globin genes, leaving only one intact and active alpha-globin gene. People with Hb H disease usually have moderate anaemia, but are generally thought to be asymptomatic. Some Hb H disease patients require transfusions, and there are reports of fetuses with Hb H disease who have severe anaemia in utero resulting in fatal hydrops foetalis syndrome. We now report a case of Hb H hydrops foetalis syndrome, caused by the inheritance of a hitherto novel alpha-globin gene point mutation (codon 35 TCC-->CCC or serine-->proline) and an alpha-thalassaemia deletion of the Filipino type removing all zeta-alpha-globin genes on the other chromosome 16. The infant was delivered prematurely because of pericardial effusion and fetal distress, and was found to have severe anaemia and congenital anomalies. A review of the relevant literature on this syndrome is presented, and serves to underscore the phenotypic variations of Hb H disease and the need for surveillance for this condition among newborns and genetic counselling in communities with a high proportion of at-risk populations.- - - - - - - - - - ranking = 5keywords = sea (Clic here for more details about this article) |
10/52. Interaction of the alpha2 polyadenylation signal mutation (AATAAA-->AATA--) and alpha0-thalassemia (--SEA), resulting in Hb H disease in a Thai patient.We report a Thai boy with a compound heterozygosity for the alpha2 polyadenylation signal mutation (AATAAA-->AATA--) and alpha0-thalassemia (--SEA), who suffered from Hb H disease with more severe clinical symptoms than those usually observed with deletional Hb H disease. His Hb H level was as high as 52% of total hemoglobin. The hematologic data of this unusual case of Hb H disease was compared with those of Hb H disease with a homozygosity for the alpha2 polyadenylation signal mutation, and compound heterozygosity of the alpha2 polyadenylation signal mutation and alpha0-thalassemia. A simple dna assay based on an allele specific polymerase chain reaction for the detection of this polyadenylation signal mutation is described.- - - - - - - - - - ranking = 8keywords = sea (Clic here for more details about this article) |
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