Hb H Disease Caused by a Homozygosity for the AATAAA→ AATAAG Mutation in the Polyadenylation Site of the α2-Globin Gene: Hematological Observations

Fei, You-Jun; Öner, Reyhan; Bozkurt, G.; Gu, Lihao; Altay, Çiğdem; Gürgey, Aytemiz; Fattoum, S.; Baysal, E.; Huisman, T. H. J.

doi:10.1159/000204657

Cited by 33 publications

(13 citation statements)

References 8 publications

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“…Furthermore, it is quite evident that in combination with the α TSaudi mutation it provokes the phenotype of HbH disease. The diagnosis of HbH disease is in accordance with previous reports, showing that the α TSaudi mutation discloses a severe thalassaemic potential and can evoke HbH disease in homozygosity or in compound heterozygosity with other mutations (8–10). Other family members, heterozygous carriers of either the α TSaudi mutation (III‐1 and 2) or the unknown deletion (I‐1), had the expected haematological phenotype of mild heterozygous α‐thalassaemia.…”

Section: Discussionsupporting

confidence: 90%

“…Specifically, the degree of chain unbalance, as measured by globin chain biosynthesis in reticulocytes and in BM erythroid cells in patient II‐1, has been estimated to be much lower than normally seen in patients with HbH disease caused by the /α TSaudi α genotype. It is well documented from the literature and the clinical experience that the α TSaudi mutation causes a sharp imbalance in the globin chain synthesis with an in vitro β/α average specific activity ratio of 2.13 in heterozygosity and of 3.9 in the homozygous state (8, 11). An even greater disturbance of the globin synthesis is expected from the combined heterozygosity of a mutation with such a severe thalassaemic potential, with an extended deletion in trans .…”

Section: Discussionmentioning

confidence: 99%

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A novel case of haemoglobin H disease associated with clinical and morphological characteristics of congenital dyserythropoietic anaemia type I

Antonelou¹,

Papassideri²,

Karababa³

et al. 2002

European J of Haematology

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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.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

A novel case of haemoglobin H disease associated with clinical and morphological characteristics of congenital dyserythropoietic anaemia type I

Antonelou¹,

Papassideri²,

Karababa³

et al. 2002

European J of Haematology

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“…Sequencing of the β‐globin genes confirmed heterozygosity for the IVS‐I‐6 (T>C) β + point mutation, a condition compatible with the haematological picture. Gap‐PCR excluded common deletion defects and triplications of the α genes in this case but direct sequencing, performed because of the ethnicity of the patient, revealed two different α2 polyadenylation site (polyA) mutations, the AAT A AA>AAT G AA (8) and AATAA A >AATAA G (9). No inclusion bodies were detected.…”

Section: Resultsmentioning

confidence: 87%

α‐thalassaemia masked by β gene defects and a new polyadenylation site mutation on the α2‐globin gene

Harteveld

Oosterhuis²,

Schoenmakers

et al. 2010

European J of Haematology

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We report three examples of chronic anaemia involving complex combinations of alpha- and beta-globin gene defects. The first case had a potential Hb H disease caused by the classic SEA/RW deletions masked by Hb E [beta26(B8)Glu-->Lys] in the homozygous state. The second had an unusual Hb H disease caused by compound heterozygosity for two different alpha2 polyadenylation site mutations masked by a beta-thalassaemia heterozygosity. The third had an intermediate alpha-thalassaemia with considerable anaemia caused by an as yet unknown polyadenylation site (AATAAA>AATAAC) mutation in combination with a common RW deletion masked by a common Hb C [beta6(A3)Glu-->Lys] heterozygosity. Diagnostic methods, genotype/phenotype correlations and the chance of overlooking these combinations during risk assessment in a multiethnic society are discussed.

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“…Our results may suggest that the frequency of the ÀÀ MED-I allele among Iranians decreases from west to east, while the frequency of the poly A signal mutation increases. Only one allele was an AATAAA!AATGAA transition, previously described as a T-Turkish a (24), also found in the Middle East (25) and Greece (24,26). Six alleles were AATAAA!AATAAG transitions, a mutation found in Eastern Saudi Arabia and Kuwait and known as a T-Saudi a (5,22,23).…”

Section: Discussionmentioning

confidence: 94%

Molecular Basis of Hb H Disease in Southwest Iran

Yavarian¹,

Karimi²,

Zorai³

et al. 2005

LHEM

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Although alpha0-thalassemia (thal) defects are not very frequent in the Iranian population, Hb H disease does occur in the country. We have analyzed the alpha gene cluster of 13 patients showing the presence of Hb H to establish the molecular background of this disease in southwest Iran (Shiraz and Hormozgan provinces). Using gap-polymerase chain reaction (gap-PCR) and direct DNA sequencing we have found the --MED-I deletion, the polyadenylation signal (poly A) mutations alphaT-Saudi alpha and alphaT-Turkish alpha and Hb Constant Spring (Hb CS) in association with the common -alpha3.7 deletion. This study has revealed that: 1) at least six genotypes are responsible for Hb H disease in the area: .-alpha3.7/ --MED-I; -alpha3.7/alphaT-Saudi alpha; alphaT-Saudi alpha/alphaT-Saudi alpha; alphaCSalpha/--MED-I; --MED-I/alphaT-Turkish alpha; and the atypical forms of Hb H disease -alpha3.7/alphaCSalpha. 2) The molecular background of Hb H disease in the southwest area of Iran is more similar to the Mediterranean type than to the Southeast Asian. 3) Hb Bart's hydrops fetalis syndrome and mild, intermediate or severe postnatal Hb H disease conditions can be expected, but at a relatively low incidence. 4) The diagnostic flowchart for patients with microcytic hypochromic anemia should include iron deficiency, beta-thal, alpha+- and alpha0-thal analyses.

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Hb H Disease Caused by a Homozygosity for the AATAAA→ AATAAG Mutation in the Polyadenylation Site of the α2-Globin Gene: Hematological Observations

Cited by 33 publications

References 8 publications

A novel case of haemoglobin H disease associated with clinical and morphological characteristics of congenital dyserythropoietic anaemia type I

A novel case of haemoglobin H disease associated with clinical and morphological characteristics of congenital dyserythropoietic anaemia type I

α‐thalassaemia masked by β gene defects and a new polyadenylation site mutation on the α2‐globin gene

Molecular Basis of Hb H Disease in Southwest Iran

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