An Initiation Codon Mutation as a Cause of a β-Thalassemia

Abstract

During the course of a screening program for beta-thalassemia mutations among beta-thalassemia heterozygotes in Yugoslavia we observed a mutation (ATG----ACG) in the initiation codon of the beta-globin gene which has not been described before. The abnormality was initially detected through mapping of the beta-globin gene by Southern blot analysis using the restriction enzyme Nco I. The loss of the Nco I site resulted in the presence of an 8.3 kb band in addition to the normal 5.2 kb band. The mutation was identified by sequence analysis of amplified DNA and by dot-blot analysis of this DNA with a 32P-labeled oligonucleotide probe. An additional polymorphism (CAC----CAT) was present at codon 2 on the same chromosome; this mutation was detected by Orkin et al in 1982 (1). Hematological and in vitro chain synthesis data suggest that the beta-thalassemia is of the beta zero type.

Omenn syndrome due to ARTEMIS mutations

“…Heterozygous mutations of the initiation codon of the beta-globin gene can result in ␤-thalassemia. 41,42 V(D)J recombination efficiency in primary dermal patient's fibroblasts was present to a level of about 25% of wild-type efficiency, supporting the notion that residual ARTEMIS function is present in cells of the patient.…”

Beta-thalassaemia in indigenous Belgian families: identification of a novel mutation

“…Surprisingly, we found the T→C transition at the initiation codon in two unrelated families. The incidence of this mutation is supposed to be low, since it has only occasionally been described (Jankovic et al 1990;Beris et al 1993). The results obtained with this group of Belgian patients suggest that it could be more common.…”

An A-to-C substitution involving the translation initiation codon in a patient with myophosphorylase deficiency (McArdle's disease)

“…Point mutations in the translation initiation codon have been described in several other inherited diseases: for example, mutations to ACG, to GTG, and to ATA in the P-globin gene causing P-thalassemia (Jankovic et al, 1990;Hattori et al, 1991;Saba et al, 1992), a mutation to ATA in the phenylalanine hydroxylase gene causing phenylketonuria (Eiken et al, 1992), and mutations to G T G and to ACG in the P-hexosaminidase a-subunit gene causing Tay-Sachs disease (Mules et al, 1992;Harmon et al, 1993). The unusual association of McArdle's disease and scleroderma raises the question of a possible common pathogenetic mechanism.…”