The polyadenylation site mutation in the alpha-globin gene cluster

In a previous study, we described a form of nondeletion alpha- thalassemia (alpha T Saudi alpha) found in subjects of Saudi Arabian origin. In the current study, using synthetic oligoprobe hybridization and restriction enzyme analysis, we have demonstrated that the molecular basis of alpha T Saudi alpha is due solely to a single base mutation (AATAAA----AATAAG) in the polyadenylation signal of the alpha 2 gene and that the frameshift mutation in codon 14 of the linked alpha 1 gene is the result of a cloning artefact. The alpha 2 polyadenylation signal mutation occurs in other Middle Eastern and the Mediterranean populations and is responsible for the clinical phenotype of Hb H disease in some Saudi Arabian individuals with five alpha genes (alpha T Saudi alpha/(alpha alpha alpha)T Saudi). Evidence suggests that the (alpha alpha alpha)T Saudi haplotype has arisen as a result of a recombination between two misaligned chromosomes bearing the alpha T Saudi alpha defect.

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The polyadenylation site mutation in the alpha-globin gene cluster

Blood ◽

10.1182/blood.v71.2.313.313 ◽

1988 ◽

Vol 71 (2) ◽

pp. 313-319 ◽

Cited By ~ 47

Author(s):

SL Thein ◽

RB Wallace ◽

L Pressley ◽

JB Clegg ◽

DJ Weatherall ◽

...

Keyword(s):

Middle Eastern ◽

Globin Gene ◽

Saudi Arabian ◽

Polyadenylation Signal ◽

Enzyme Analysis ◽

Restriction Enzyme Analysis ◽

Site Mutation ◽

Mediterranean Populations ◽

Alpha Globin ◽

Hb H Disease

Abstract In a previous study, we described a form of nondeletion alpha- thalassemia (alpha T Saudi alpha) found in subjects of Saudi Arabian origin. In the current study, using synthetic oligoprobe hybridization and restriction enzyme analysis, we have demonstrated that the molecular basis of alpha T Saudi alpha is due solely to a single base mutation (AATAAA----AATAAG) in the polyadenylation signal of the alpha 2 gene and that the frameshift mutation in codon 14 of the linked alpha 1 gene is the result of a cloning artefact. The alpha 2 polyadenylation signal mutation occurs in other Middle Eastern and the Mediterranean populations and is responsible for the clinical phenotype of Hb H disease in some Saudi Arabian individuals with five alpha genes (alpha T Saudi alpha/(alpha alpha alpha)T Saudi). Evidence suggests that the (alpha alpha alpha)T Saudi haplotype has arisen as a result of a recombination between two misaligned chromosomes bearing the alpha T Saudi alpha defect.

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Prolonged Pyrexia: Kikuchi-Fujimoto Disease in a Patient With Hb H-Constant Spring Thalassemia

Clinical Medicine Insights Case Reports ◽

10.1177/1179547620936424 ◽

2020 ◽

Vol 13 ◽

pp. 117954762093642

Author(s):

Ganesh Kasinathan

Keyword(s):

Dna Analysis ◽

Complete Blood Count ◽

Globin Gene ◽

Oral Prednisolone ◽

Lymph Node Biopsy ◽

Whole Body ◽

Gene Deletions ◽

Prolonged Fever ◽

Alpha Globin ◽

Hb H Disease

Introduction: Haemoglobin H (Hb H) disease is an alpha thalassemia characterised by either 3 alpha-globin gene deletions (deletional type) or 2 alpha-globin gene deletions with 1-point mutation (nondeletional type). Haemoglobin H-Constant Spring thalassemia is the most common Hb H disease in Asia. Kikuchi-Fujimoto disease (KFD) is an important cause of prolonged fever in thalassemia and is often self-limiting. Case Presentation: A 30-year-old women of Malay ethnicity presented to the thalassemia unit with a month history of prolonged fever, headache, and painful enlarged neck lymph nodes. She is known to have Hb H-Constant Spring thalassemia, in which she is on 3-monthly blood transfusion. Physical examination revealed persistent pyrexia of 38°C. She had multiple tender bilateral cervical lymphadenopathies with the largest measuring 4 × 4 cm. The complete blood count revealed hypochromic microcytic anaemia with leucopenia and a normal platelet count. She had hyperferritinemia of 3500 ng/mL. The DNA analysis of alpha-globin gene showed heterozygosity for alpha zero thalassemia South East Asian deletion with termination codon mutation (TAA-CAA) which was consistent with Hb H-Constant Spring thalassemia. Numerous investigations for her prolonged fever including cultures did not yield any positive results. Whole-body computed tomography (CT) imaging showed diffuse lymphadenopathies and hepatosplenomegaly. Finally, a left cervical lymph node biopsy was performed which was consistent with KFD. She was treated with oral prednisolone which was gradually tapered based on response. Currently, she is asymptomatic and is in complete remission. Conclusion: Kikuchi-Fujimoto disease should be considered as a cause for prolonged pyrexia in a patient with thalassemia. An early diagnosis of KFD would avoid an unnecessary battery of investigations. This case highlights the importance of clinicopathological correlation in managing patients with thalassemia as these patients often have other associated morbidities.

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Restriction enzyme analysis of the β-globin gene in DNA from β°-thalassaemic subjects from Ferrara

Biochemical and Biophysical Research Communications ◽

10.1016/0006-291x(79)91557-2 ◽

1979 ◽

Vol 91 (2) ◽

pp. 548-553 ◽

Cited By ~ 4

Author(s):

L. Del Senno ◽

F. Conconi ◽

P.F.R. Little ◽

R. Williamson

Keyword(s):

Restriction Enzyme ◽

Globin Gene ◽

Enzyme Analysis ◽

Restriction Enzyme Analysis

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Molecular basis of hemoglobin-H disease in the Mediterranean population

Blood ◽

10.1182/blood.v54.6.1434.bloodjournal5461434 ◽

1979 ◽

Vol 54 (6) ◽

pp. 1434-1438

Author(s):

YW Kan ◽

AM Dozy ◽

G Stamatoyannopoulos ◽

MG Hadjiminas ◽

Z Zachariades ◽

...

Keyword(s):

Molecular Basis ◽

Gene Deletion ◽

Globin Gene ◽

Mediterranean Population ◽

Mediterranean Populations ◽

Alpha Thalassemia ◽

Alpha Globin ◽

The Mediterranean ◽

Endonuclease Mapping ◽

Hemoglobin H Disease

We investigated the molecular basis of hemoglobin-H disease by hybridization and restriction endonuclease mapping of the DNA in the Mediterranean populations. Of the 12 patients studied from Cyprus and Sardinia, 8 had the typical deletion defect with a single remaining alpha-globin gene. The nondeletion type of alpha-thalassemia was found in 3, and a “dysfunctional” gene in one. We conclude that the predominant cause of alpha-thalassemia in these populations is gene deletion.

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Molecular basis of hemoglobin-H disease in the Mediterranean population

Blood ◽

10.1182/blood.v54.6.1434.1434 ◽

1979 ◽

Vol 54 (6) ◽

pp. 1434-1438 ◽

Cited By ~ 29

Author(s):

YW Kan ◽

AM Dozy ◽

G Stamatoyannopoulos ◽

MG Hadjiminas ◽

Z Zachariades ◽

...

Keyword(s):

Molecular Basis ◽

Gene Deletion ◽

Globin Gene ◽

Mediterranean Population ◽

Mediterranean Populations ◽

Alpha Thalassemia ◽

Alpha Globin ◽

The Mediterranean ◽

Endonuclease Mapping ◽

Hemoglobin H Disease

Abstract We investigated the molecular basis of hemoglobin-H disease by hybridization and restriction endonuclease mapping of the DNA in the Mediterranean populations. Of the 12 patients studied from Cyprus and Sardinia, 8 had the typical deletion defect with a single remaining alpha-globin gene. The nondeletion type of alpha-thalassemia was found in 3, and a “dysfunctional” gene in one. We conclude that the predominant cause of alpha-thalassemia in these populations is gene deletion.

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