Mild Hb S-β+-Thalassemia with a Deletion of Five Nucleotides at the Polyadenylation Site of the β-Globin Gene

Hemoglobin ◽  
2003 ◽  
Vol 27 (4) ◽  
pp. 257-260 ◽  
Author(s):  
Philippe Lacan ◽  
Bénédicte Ponceau ◽  
Martine Aubry ◽  
Alain Francina
Keyword(s):  
Globin Gene ◽  
Polyadenylation Site ◽  
Hb S

A novel AATAAACATAAA mutation at the polyadenylation site of the beta-globin gene

2001 ◽  
Vol 115 (1) ◽  
pp. 231-231
Author(s):  
S. K. Ma ◽  
A. C. W. Lee ◽  
A. Y. Y. Chan ◽  
L. C. Chan
Keyword(s):  
Globin Gene ◽  
Polyadenylation Site ◽  
Beta Globin ◽  
Beta Globin Gene

Hemoglobin San Martin: A New Unstable Variant Associated with Hemoglobin S in an Argentinean Boy.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3806-3806 ◽  
Author(s):  
Aurora Feliu-Torres ◽  
S. Eandi-Eberle ◽  
K. Calvo ◽  
I. Bragós ◽  
M. Ojeda ◽  
...  
Keyword(s):  
Globin Gene ◽  
Normal Pregnancy ◽  
Exon 2 ◽  
Hydrophobic Residues ◽  
Dark Urine ◽  
External Position ◽  
Exon 1 ◽  
History Of ◽  
Hb S ◽  
San Martín

Abstract A new unstable hemoglobin (Hb) detected in a 10 year-old boy from San Martin, Buenos Aires, Argentina, is hereby described. The patient (pt) was born at term, after a normal pregnancy, by cesarean section. He had a history of multiple episodes of pallor, jaundice and dark urine related to infections, since 6 months of age. The physical examination only revealed pallor and icterus, with no hepatosplenomegaly. The pt and his mother showed the presence of an anomalous band on both alkaline and acid pH electrophoresis. Isopropanol and sickling tests were positive. In order to identify the abnormal Hb variant the β globin gene was analysed. Three exons were amplified and automatically sequenced with direct and reverse probes. Table 1. Hematological data Patient Mother Hb g/dl/PCV % 10.9/36 10.5/34 MCV fl/MCH pg 79.4/24.1 80.7/24.6 RDW % 15.7 18.2 Reticulocyte count % 5.2 8.0 Electrophoresis (pH 9) A/X/A2 A/X/A2 Electrophoresis (pH 5) X/A-A2 X/A-A2 Sickling/Isopropanol tests Positive/Positive Positive/Positive Inclusion bodies Positive Positive Two mutations were identified in the same β globin gene. One in Exon 1, corresponding to Hb S [Ex1 β6 Glu→Val (GAG→GTG)]; and the second one in Exon 2 [Ex2 β85 (F1) Phe→Leu (TTT→CTT)]. This second mutation is responsible for a new unstable Hb that has not been described so far, in association with Hb S. The substitution occurs in an external position between two hydrophobic residues of different size.

scholarly journals Hemoglobins in Togolese Newborns: Hb S, Hb C, Hb Bart's, and α-Globin Gene Status

1998 ◽  
Vol 59 (3) ◽  
pp. 208-213 ◽  
Author(s):  
Akueté Yvon Segbena ◽  
Claude Prehu ◽  
Henri Wajcman ◽  
Josiane Bardakdjian-Michau ◽  
Kodjovi Messie ◽  
...  
Keyword(s):  
Globin Gene ◽  
Hb S ◽  
Gene Status ◽  
Hb Bart's ◽  
Hb C

scholarly journals DNA sequence variation in a negative control region 5' to the beta- globin gene correlates with the phenotypic expression of the beta s mutation

Blood ◽  
1992 ◽  
Vol 79 (3) ◽  
pp. 787-792 ◽  
Author(s):  
J Elion ◽  
PE Berg ◽  
C Lapoumeroulie ◽  
G Trabuchet ◽  
M Mittelman ◽  
...  
Keyword(s):  
Dna Sequence ◽  
Sickle Cell ◽  
Globin Gene ◽  
Phenotypic Expression ◽  
Fetal Hemoglobin ◽  
Negative Control ◽  
Globin Genes ◽  
Beta Globin ◽  
Beta Globin Gene ◽  
Hb S

The clinical diversity of sickle cell anemia is strongly related to the degree of intracellular hemoglobin S (Hb S) polymerization, which in turn is dependent on the intracellular concentration of Hb S. We have recently defined a region of DNA approximately 500 bp 5′ to the human beta-globin gene that acts as a silencer for the transcription of this gene and have shown that a polymorphism in this sequence is associated with a thalassemic phenotype of the beta-globin gene. In this work we have examined the correlation of DNA sequence polymorphisms in this silencer with binding of a previously identified putative repressor protein, BP1, and with the expression of Hb S in individuals heterozygous for the beta s allele. It was found that specific configurations of the motif, (AT)x(T)y, are homogeneous for the major haplotypes of the beta-globin gene cluster described on beta s chromosomes. Binding of BP1 was measured to DNA of three haplotypes: Indian, Benin, and Bantu. BP1 binds most tightly to DNA of the Indian haplotype, and these patients produce less beta s protein than Benin patients, whose DNA exhibits weaker affinity for BP1. Binding of BP1 is the weakest to DNA of the Bantu haplotype, which is associated with clinically more severe sickle cell symptoms. These data are consistent with the hypothesis that these polymorphisms may not be neutral and that the DNA sequence at this site may affect the expression of the beta s gene. Such an effect may be synergistic with other genetic variables, such as fetal hemoglobin levels, F-cell numbers, and the number of alpha-globin genes, in determining intracellular polymerization and, thus, the severity of the sickle cell syndromes.

Hb S [β6(A3)Glu→Val, GAG>GTG] and β-Globin Gene Cluster Haplotype Distribution in Mauritania

Hemoglobin ◽  
2012 ◽  
Vol 36 (4) ◽  
pp. 311-315 ◽  
Author(s):  
Fatimetou M. Veten ◽  
Isselmou O. Abdelhamid ◽  
Ghlana M. Meiloud ◽  
Sidi M Ghaber ◽  
Mohamed L. Salem ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Globin Gene ◽  
Globin Gene Cluster ◽  
Haplotype Distribution ◽  
Hb S

scholarly journals A novel A ATAAA→ C ATAAA mutation at the polyadenylation site of the β-globin gene

2001 ◽  
Vol 115 (1) ◽  
pp. 231-231
Author(s):  
S. K. Ma ◽  
A. C. W. Lee ◽  
A. Y. Y. Chan ◽  
L. C. Chan
Keyword(s):  
Globin Gene ◽  
Polyadenylation Site

scholarly journals Hemoglobin C/Korle-Bu Identified In A Patient With A Previous Diagnosis Of Hemoglobin S/C Disease

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S110-S111
Author(s):  
D Dolezal ◽  
C Tormey ◽  
H Rinder ◽  
A J Siddon
Keyword(s):  
Cellulose Acetate ◽  
Hospital Admissions ◽  
Globin Gene ◽  
Clinical Manifestations ◽  
Gene Sequencing ◽  
American Woman ◽  
Target Cells ◽  
Hemoglobin C ◽  
Hb S ◽  
Hb C

Abstract Casestudy Hemoglobin Korle-Bu (Hb-KB) is an uncommon Hb variant that can be mistaken for Hb-S on electrophoretic screening. While Hb-KB alone has no clinical manifestations, there are only limited case studies describing KB in combination with other Hb variants. Here we report a rare case of Hb-C/KB misdiagnosed and managed as Hb-S/C disease for over 20 years. Results A 21-year-old African American woman with presumed Hb-S/C disease presented with generalized abdominal pain, nausea, and vomiting. In 1999, Hb electrophoresis showed 59% of abnormal hemoglobin presumed to be HbS and 41% HbC+A2; agar/acetate gel analysis was not employed and the hemoglobinopathy remained incompletely characterized. She had a history of back, chest, abdomen, and extremity pains requiring multiple hospital admissions, with treatments including dilaudid, oxycontin, oxycodone, and hydroxyurea. Her vital signs were normal and her examination was only significant for abdominal tenderness. Imaging studies did not show any evidence vascular occlusion, avascular necrosis, or end-organ dysfunction. RBC indices were remarkable for mild borderline anemia, microcytosis, decreased MCH/elevated MCHC, and borderline elevated RDW. Peripheral smear showed microcytic red cells with anisocytosis, scattered target cells, and a notable absence of sickled cells and Hb-C-crystals. The diagnosis of Hb-S/C disease was then revisited. HPLC showed abnormal hemoglobins in the Hb-D window at 55.1% and in the Hb-C window at 40.6%, with 3.5% Hb-A2 and no normal Hb-A. Gel electrophoresis with cellulose acetate followed by citrate agar suggested Hb-C in combination with either D, G, or Korle-Bu. Definitive diagnosis was obtained by beta globin gene sequencing that demonstrated one copy Hb-C (19G>A, Glu7Lys) and one copy Hb- Korle-Bu (220G>A, Asp74Asn). Given the absence of Hb-S/C disease, her gastrointestinal distress and pain episodes were re-evaluated. Conclusion Hb-S and Hb-Korle-Bu migrate similarly in cellulose acetate electrophoresis but can be distinguished on citrate agar. Challenging beta chain variants can now be readily differentiated by complete gene sequencing. This case study emphasizes the importance of distinguishing Hb-KB from clinically-significant Hb-S.

scholarly journals Acute pancreatitis in a child with sickle cell anemia

2020 ◽  
Vol 7 (5) ◽  
pp. 1174
Author(s):  
Manoj Kumar D. ◽  
Komalatha Choppari ◽  
Suresh R. J. Thomas
Keyword(s):  
Amino Acid ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Globin Gene ◽  
Red Blood Cell Transfusion ◽  
Beta Globin ◽  
Cell Disease ◽  
Chromosome 11 ◽  
Molecular Stability ◽  
Hb S

Sickle cell disease (SCD) is a term used for a group of genetic disorders characterized by production of Hb “S”. Sickle cell hemoglobin opathy occurs due to mutation of beta-globin gene situated on short arm of chromosome 11, where adenine is replaced by thymine in base of DNA coding for the amino acid in the sixth position in beta-globin chain. This leads to an amino acid change in beta chain of Hb molecule, from glutamic acid to valine. The result is profound change in the molecular stability and solubility of Hb “S”. Authors are reporting a 8-year-old girl who is a known case of sickle cell disease presented with complaints of intermittent pain abdomen and vomiting since 30 days. Investigations revealed elevated pancreatic enzymes with radiological evidence of pancreatitis. Packed red blood cell transfusion and appropriate supportive therapy given and child recovered well.

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