GM07425

GM07425 LCL from B-Lymphocyte

Description:

BETA-THALASSEMIA
HEMOGLOBIN--BETA LOCUS; HBB

Affected:

Yes

Sex:

Male

Age:

12 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases

Class

Mutations of the Hemoglobin Loci

Biopsy Source

Peripheral vein

Cell Type

B-Lymphocyte

Tissue Type

Blood

Transformant

Epstein-Barr Virus

Sample Source

LCL from B-Lymphocyte

Race

White

Relation to Proband

proband

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

Mediterranean; B-thalassemia; donor subject is a compound heterozygote: one allele has a G>A change at position 110 of intron 1 in the HBB gene [IVS1,G>A,+110 (beta plus)]; the second allele has a nonsense mutation, changing the beta-39 codon from glutamine to a stop codon [Gln39Ter (Q39X), beta zero]

Characterizations

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by Nucleoside Phosphorylase, Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis

Gene

HBB

Chromosomal Location

11p15.5

Allelic Variant 1

141900.0364; BETA-PLUS-THALASSEMIA

Identified Mutation

IVS1, G>A, +110; A G-to-A change at position 110 of IVS-1 was found in a Mediterranean patient by Spritz et al. (1981) and Westaway and Williamson (1981). The mutation created a new splice acceptor site. Kaplan et al. (1990) studied the molecular basis of beta-thalassemia minor, which has a frequency of about 1% among French Canadians residing in Portneuf County of Quebec Province. They showed that there were 2 different beta-thalassemia mutations segregating in the population: an RNA processing mutation involving nucleotide 110 of IVS-1 on haplotype 1 and a point mutation leading to chain termination through a nonsense codon at position 39 (141900.0312), occurring on haplotype 2.

Gene

HBB

Chromosomal Location

11p15.5

Allelic Variant 2

141900.0312; BETA-ZERO-THALASSEMIA

Identified Mutation

GLN39TER; Chehab et al. (1986) found evidence for new mutation in the codon at beta-39 from CAG (glutamine) to the stop codon TAG. The beta-39 nonsense mutation is the second most common beta-thalassemia lesion in Italy, accounting for a third of cases, and the most common in Sardinia, accounting for 90% of cases there. In Sardinia, the beta-39 mutation has been identified with 9 different haplotypes. All this suggested to Chehab et al. (1986) that beta-39 is a mutational hotspot. Trecartin et al. (1981) found that the form of beta-zero-thalassemia that is predominant in Sardinia is caused by a single nucleotide mutation at the position corresponding to amino acid number 39 and converting a glutamine codon (CAG) to an amber termination codon (UAG). (Epstein et al. (1963) described 'amber' mutants of phage T4 in a frequently cited paper in a Cold Spring Harbor Symposium on Quantitative Biology. The origin of the unusual name 'amber' is, as Witkowski (1990) called it, 'an interesting footnote in the history of molecular biology.' Edgar (1966) recounted that R. H. Epstein and C. M. Steinberg, then at the California Institute of Technology, had promised Harris Bernstein, then at Yale University, that the mutants, if any were found, would be named after his mother. They were found and were named 'amber,' the English equivalent of 'Bernstein.' The other 2 'stop' codons, UGA and UAA, are sometimes referred to as 'opal' and 'ochre,' respectively.) Rosatelli et al. (1992) used denaturing gradient gel electrophoresis (DGGE) followed by direct sequence analysis of amplified DNA to study 3,000 beta-thalassemia chromosomes in the Sardinian population. They confirmed that the predominant mutation, present in 95.7% of beta-thalassemia chromosomes, was gln39-to-ter.