1/10. 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 = 1keywords = anaemia (Clic here for more details about this article) |
2/10. 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 = 3keywords = anaemia (Clic here for more details about this article) |
3/10. Hb H hydrops fetalis syndrome associated with the interaction of two common determinants of alpha thalassaemia (--MED/(alpha)TSaudi(alpha)).To date, more than 35 single or oligonucleotide mutations of the alpha genes that cause alpha thalassaemia have been described. Their interactions give rise to widely variable clinical manifestations, from a mild hypochromic, microcytic anaemia to a lethal intrauterine anaemia associated with hydrops fetalis. Understanding the molecular genetics enables accurate genotyping, genetic counselling and prenatal testing for the most severe forms of alpha thalassaemia. Here we show for the first time that the interaction between two relatively common forms of alpha thalassaemia (--MED/(alpha)TSaudi(alpha)) may be associated with a clinically severe form of alpha thalassaemia, Hb H hydrops fetalis.- - - - - - - - - - ranking = 2keywords = anaemia (Clic here for more details about this article) |
4/10. A novel case of haemoglobin H disease associated with clinical and morphological characteristics of congenital dyserythropoietic anaemia type I.We report, for the first time, an unusual case of congenital anaemia with the clinical diagnosis of haemoglobin H disease complicated by morphological features at the light and electron microscopy level very similar to those of CDA-I. The red cell indices and the globin chain biosynthetic ratio were not characteristic of the defective haemoglobin genotype. The haematological, clinical and morphological data strongly suggest the novel coexistence of the two defects in a patient. The disease is characterised by a unique dyserythropoietic phenotype of diagnostic importance, which possibly brings new data regarding the reciprocal interaction between the two diseases, especially concerning a specific abnormality in globin chain synthesis in CDA-I, as previously suggested.- - - - - - - - - - ranking = 5keywords = anaemia (Clic here for more details about this article) |
5/10. Human alpha2-globin nonsense-mediated mRNA decay induced by a novel alpha-thalassaemia frameshift mutation at codon 22.We describe a novel alpha-thalassaemia determinant in a 3-year-old girl presenting a mild microcytic and hypochromic anaemia, and normal haemoglobin A2 level. Molecular studies revealed heterozygosity for a novel microdeletion (-C) at codon 22 of the alpha2-globin gene. As the frameshift mutation generates a premature translation termination codon at position 48/49, we investigated the effect of the nonsense codon on the alpha2-globin gene expression. Although it does not affect rna splicing, the premature nonsense codon induces accelerated mRNA degradation. To our knowledge, this is the first time the nonsense-mediated mRNA decay has been reported to occur in human alpha-globin mRNA.- - - - - - - - - - ranking = 1keywords = anaemia (Clic here for more details about this article) |
6/10. Haemoglobin-H disease presenting with microcytic hypochromic anaemia in an 81 year old woman.Over an 11 year period, the diagnosis of haemoglobin-H (Hb-H) disease was missed in a Caucasian woman of British stock who first presented with microcytic hypochromic anaemia at the age of 81. The diagnosis was confirmed at the age of 92, when the typical inclusions of Hb-H disease were demonstrated in erythrocytes stained with brilliant cresyl blue, and the presence of Hb-H was documented by haemoglobin electrophoresis. She subsequently developed biliary obstruction due either to an inflammatory polyp associated with choledocholithiasis or ampullary carcinoma.- - - - - - - - - - ranking = 5keywords = anaemia (Clic here for more details about this article) |
7/10. A base substitution (T-->C) in codon 29 of the alpha 2-globin gene causes alpha thalassaemia.We have identified three individuals of Greek or Greek Cypriot origin with an atypical form of HbH disease characterized by a severe hypochromic microcytic anaemia associated with relatively small amounts of HbH in the peripheral blood. Molecular analysis has shown that each is a compound heterozygote for a previously described mutation affecting the poly a addition signal (AATAAA-->AATAAG) and a previously undescribed mutation involving a T-->C transition in codon 29 of the alpha 2 gene causing a leucine-->proline substitution. Although this mutation would be expected to produce an unstable haemoglobin and hence a haemolytic anaemia, simple heterozygotes for the alpha 29Leu-->Pro mutation have the phenotype of alpha-thalassaemia trait.- - - - - - - - - - ranking = 2keywords = anaemia (Clic here for more details about this article) |
8/10. Haemoglobin Manukau beta 67[E11] Val-->Gly: transfusion-dependent haemolytic anaemia ameliorated by coexisting alpha thalassaemia.Haemoglobin Manukau (beta 67 Val-->Gly) is a novel haemoglobin variant presenting in two brothers as nonspherocytic haemolytic anaemia which became transfusion dependent by 6 months of age. The severity of clinical expression seems to be modulated by coexisting alpha thalassaemia: the severely affected children have a normal complement of alpha globin genes with an unusual genotype (-alpha 3.7/alpha alpha alpha 3-7), while their father, who carries the abnormal gene with minimal symptoms, has homozygous alpha thalassaemia (-alpha 3.7/-alpha 3.7). Another unusual feature of this case is the association of the beta 67 Val-->Gly mutation with modification of beta 141 Leu to a residue (believed to be hydroxyleucine) that is not detected by standard amino acid analysis. This finding offers an explanation for the previous report of an association of another mutation at this site (Hb Sydney beta 67 Val-->Ala) with Hb Coventry (deletion of beta 141 Leu).- - - - - - - - - - ranking = 5keywords = anaemia (Clic here for more details about this article) |
9/10. Composition of the intra-erythroblastic precipitates in thalassaemia and congenital dyserythropoietic anaemia (CDA): identification of a new type of CDA with intra-erythroblastic precipitates not reacting with monoclonal antibodies to alpha- and beta-globin chains.Ultrathin sections of bone marrow cells from two patients with homozygous beta-thalassaemia, two patients with haemoglobin H (HbH) disease, a patient with congenital dyserythropoietic anaemia (CDA) type III and two patients with severe congenital dyserythropoietic anaemia of an unusual type were reacted with mouse monoclonal antibodies against various globin chains and the reaction visualized using a gold-labelled goat antibody against mouse IgG. The multiple rounded intra-erythroblastic inclusions found in homozygous beta-thalassaemia reacted with the monoclonal antibody against alpha-globin chains but not beta-globin chains, thus confirming that they consisted of precipitated alpha-globin chains. The branching intra-erythroblastic inclusions found in HbH disease and CDA type III reacted with the monoclonal antibody against beta-globin chains but not alpha-globin chains, indicating that they consisted of precipitated beta-globin chains. The two patients with severe CDA had been transfusion-dependent since infancy, had a normal alpha:beta globin chain synthesis ratio or parents with normal red cell indices, displayed prominent dysplastic changes in their erythroblasts, and had intra-erythroblastic inclusions resembling those seen in homozygous beta-thalassaemia. However, unlike those in beta-thalassaemia, the inclusions in these two patients did not react with the monoclonal antibody against either alpha- or beta-globin chains. The inclusions reacted with antibody against zeta-globin chains, but detailed studies in one of the patients indicated that the antigen involved was not zeta-globin. These patients have features not reported in the condition known as dominantly inherited inclusion body beta-thalassaemia and appear to suffer from a novel type of CDA in which the intra-erythroblastic inclusions may consist of some non-globin protein or structurally-abnormal alpha-globin chains.- - - - - - - - - - ranking = 6keywords = anaemia (Clic here for more details about this article) |
10/10. Atypical HbH disease in a Surinamese patient resulting from a combination of the -SEA and -alpha 3.7 deletions with HbC heterozygosity.The first case of haemoglobin H (HbH) disease in combination with haemoglobin C (HbC) is reported in a man of Surinamese origin. Only haemoglobin A (HbA) and HbC were detected by electrophoresis. The amount of HbC was much less than expected in HbC heterozygotes. The synthesis ratio (beta A beta C/alpha) indicated an alpha-thalassaemia defect with two non-functional alpha genes, which did not correlate with the degree of haemolysis and anaemia displayed by the patient. The dna analysis of the alpha-genes clusters revealed a defect combination -SEA/-alpha 3.7. The haematological data and the physiopathology of this atypical case are compared with the typical HbH disease found in a first cousin of the propositus. Data on the globin chains expression and on the formation of beta A and beta C homotetramers in HbH/HbC disease are presented.- - - - - - - - - - ranking = 1keywords = anaemia (Clic here for more details about this article) |
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