Description:
BETA-THALASSEMIA
HEMOGLOBIN--BETA LOCUS; HBB
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases |
| Quantity |
25 µg |
| Quantitation Method |
Please see our FAQ |
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Biopsy Source
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Peripheral vein
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Cell Type
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B-Lymphocyte
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Tissue Type
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Blood
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Transformant
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Epstein-Barr Virus
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Sample Source
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DNA from LCL
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Race
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East Indian
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Relation to Proband
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proband
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Confirmation
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Clinical summary/Case history
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Species
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Homo sapiens
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Common Name
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Human
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Remarks
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin confirmed by LINE assay |
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| Gene |
HBB |
| Chromosomal Location |
11p15.5 |
| Allelic Variant 1 |
141900.0071; HEMOGLOBIN E |
| Identified Mutation |
GLU26LYS (GLU27LYS; c.79G>A); See Hunt and Ingram (1961), Shibata et al. (1962), Blackwell et al. (1970), Fairbanks et al. (1980), Benz et al. (1981), and Kazazian et al. (1984). Orkin et al. (1982) reported the complete nucleotide sequence of a beta-E-globin gene. They found a GAG-to-AAG change in codon 26 as the only abnormality. Expression of the beta-E gene was tested by introducing it into HeLa cells. Two abnormalities of RNA processing were shown: slow excision of intervening sequence-1 and alternative splicing into exon 1 at a cryptic donor sequence within which the codon 26 nucleotide substitution resides. Antonarakis et al. (1982) used the Kazazian haplotype approach of analyzing DNA polymorphisms in the beta-globin cluster to present evidence that the beta-E mutation occurred at least twice in Southeast Asia, the mutation being G-to-A at the first nucleotide of codon 26. Thein et al. (1987) demonstrated that the GAG-to-AAG change could be recognized by the restriction enzyme MnlI which cleaves DNA at the sequence 3-prime-GGAG-5-prime. Rey et al. (1991) described SE disease in 3 black American children of Haitian origin. They pointed out that the disorder is probably more benign than SC disease, SO(Arab) disease, and SC(Harlem) disease, all of which have increased risk of the complications of sickling including pneumococcal sepsis.
Rees et al. (1996) reported a girl homozygous for Hb E with severe anemia and anisopoikilocytosis, who was also homozygous for pyrimidine 5-prime nucleotidase deficiency (P5N; 266120). In erythrocytes deficient for P5N the stability of the Hb E was decreased.
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| Remarks |
Clinically affected; Hemoglobin E/beta thalassemia; diagnosed at age 11 years due to fatigue and lethargy; no significant childhood illnesses; delayed growth and sexual development; heart murmur (SEM II/VII); osteopenia; blood transfusion required about age 30 years due to hemoglobin less than 6.8; progressive increase in spleen size; hemoglobin electrophoresis results: HbA = 0%, HbA2 = 0%, HbF = 46.3%, HbS = 0%, HbE = 53.7%; hemoglobin = 8.3 g/dl; MCV = 62; donor subject has a G>A change in codon 26 of the HBB gene resulting in the substitution of lysine for glutamic acid [Glu26Lys (E26K)]; normal and abnormal triplet seen at Beta 26; most likely to have deletional Beta Thalassemia; transfusion-dependent; currently on iron chelation therapy
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