GM21082

GM21082 LCL from B-Lymphocyte

Description:

BETA-THALASSEMIA
HEMOGLOBIN--BETA LOCUS; HBB

Affected:

Yes

Sex:

Male

Age:

29 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases

Biopsy Source

Peripheral vein

Cell Type

B-Lymphocyte

Tissue Type

Blood

Transformant

Epstein-Barr Virus

Sample Source

LCL from B-Lymphocyte

Race

Asian, Other

Ethnicity

VIETNAMESE/PANAMANIAN/CHINESE

Relation to Proband

proband

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

Clinically affected; Hemoglobin E/beta thalassemia; diagnosed at birth; transfusion dependent since age 3 years; iron overload; splenectomy at age 3 years; history of slow growth development with use of growth hormones for about 1 year; history of delayed sexual development with testosterone replacement for about 1 year; melanoma diagnosed at age 28 years; high frequency hearing loss; history of respiratory infections and pneumonia in childhood; hemoglobin electrophoresis results: HbA = 91.2%, HbA2 = 0%, HbF = 1.3%, HbS = 0%, HbE = 7.5%; hemoglobin = 12.4 g/dl; MCV = 84.4; 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)]; transfusion-dependent; currently on iron chelation therapy

Characterizations

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin confirmed by LINE assay

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.