The Beta-globin Gene in Sardinian Delta Beta 0-thalassemia Carries a C----T Nonsense Mutation at Codon 39

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 1984 Apr 1

PMID 6327288

Citations 4

Authors

S Guida

B Giglioni

P Comi

S Ottolenghi

C Camaschella

G Saglio

Affiliations

Soon will be listed here.

Abstract

Sardinian delta beta 0-thalassemia is an inherited syndrome characterized by the inactivity of the beta-globin gene and the persistent activity of the fetal gamma-globin genes, particularly the A gamma-globin gene. Previous mapping studies with restriction enzymes failed to show any abnormality in the non-alpha globin gene cluster. We have now examined the possibility that this syndrome might result from a single rather than two different defects. Restriction enzyme polymorphisms linked to the delta beta 0-thalassemic non-alpha globin fragments were defined providing the basis for cloning the delta beta 0-thalassemic beta-globin gene from the DNA of a heterozygous patient. This gene appears to carry a C----T single mutation causing the appearance of a stop codon at amino acid position 39 of the beta-globin gene. This mutation was previously reported in beta 0-thalassemic patients, in linkage with different haplotypes. We conclude that Sardinian delta beta 0-thalassemia is the result of two separate mutations, the former one (unknown) responsible for persistent expression of gamma-globin genes, the latter for beta 0-thalassemia.

Citing Articles

A molecular study of a family with Greek hereditary persistence of fetal hemoglobin and beta-thalassemia.

Giglioni B, Casini C, Mantovani R, Merli S, Comi P, Ottolenghi S EMBO J. 1984; 3(11):2641-5.

PMID: 6210198 PMC: 557743. DOI: 10.1002/j.1460-2075.1984.tb02187.x.

The same beta-globin gene mutation is present on nine different beta-thalassemia chromosomes in a Sardinian population.

Pirastu M, Galanello R, DOHERTY M, Tuveri T, Cao A, Kan Y Proc Natl Acad Sci U S A. 1987; 84(9):2882-5.

PMID: 3033668 PMC: 304764. DOI: 10.1073/pnas.84.9.2882.

A frequent A gamma-hereditary persistence of fetal hemoglobin in northern Sardinia: its molecular basis and hematologic phenotype in heterozygotes and compound heterozygotes with beta-thalassemia.

Ottolenghi S, Camaschella C, Comi P, Giglioni B, Longinotti M, Oggiano L Hum Genet. 1988; 79(1):13-7.

PMID: 2452784 DOI: 10.1007/BF00291702.

Analyses of linked beta-globin genes suggest that nondeletion forms of hereditary persistence of fetal hemoglobin are bona fide switching mutants.

Metherall J, Gillespie F, Forget B Am J Hum Genet. 1988; 42(3):476-81.

PMID: 2450454 PMC: 1715159.

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