A β°‐thalassaernia due to a 1605 bp deletion of the 5‘β‐globin gene region

Abstract

We studied a heterozygous beta zero-thalassaemia patient from Croatia with an unusually high Hb A2 level of 7.6% and an elevated Hb F level of 5.8%. The same condition was found in his father (Hb A2 8.2%; Hb F 8.5%). Gene mapping and direct sequencing analyses revealed a new deletion of 1605 bp in the 5' beta-globin gene region between positions -984/5 and +620/1. This deletion has not been observed among more than 500 beta-thalassaemia chromosomes from the Balkan countries studied in our laboratory.

A novel 105 basepair deletion causing ?0-thalassemia in members of a Thai family

“…In comparison with a Thai 3.5 kb deletion, which removes the 5Ј ␤-globin gene including the promoter sequences, the average HbA 2 level for 10 persons is 6.4% with a range of 5.5 to 7.8%. However, the HbA 2 level of the subject heterozygous for this 105 bp deletion is not unusually high as found in other relatively large deletions of the 5Ј ␤-globin gene region [16,17]. These findings suggest that the loss of not only the promoter sequences but also the region 3Ј to the TATA box of the ␤-globin gene affects the transcription of the ␦-globin gene with variable efficiency probably because of impaired interaction of LCR with the ␤-globin locus.…”

“…Recently, nearly 200 mutations have been characterized to produce ␤-thalassemia, which are mostly caused by point mutations [16]. There are 10 deletional forms of ␤-thalassemia that have been reported, ranging from 44-12622 bp [17][18][19]. In nine of them, the deletion regions have in common the 5Ј ␤-gene promoters, which exhibited an unusually high level of HbA 2 in the heterozygous state.…”

“…In nine of them, the deletion regions have in common the 5Ј ␤-gene promoters, which exhibited an unusually high level of HbA 2 in the heterozygous state. Several hypotheses have been proposed to explain the increased expression of the ␦-globin gene observed in these deletions, such as altered chromatin structure, 3Ј ␤-globin gene enhancer juxtaposition, altered competition of the remaining ␥and ␦-globin gene promoters for limited transcription factors or altered competition of the ␥-, ␦-, and ␤-globin gene promoters for the LCR sequences [17].…”

In vitro expression of β-thalassaemia gene (IVS1-1G>C) reveals complete inactivation of the normal 5' splice site and alternative aberrant RNA splicing

“…Some cases of mRNA-de¢cient b-thalassaemia involve large deletions 7 or rearrangements of the b-globin genes; however, most cases are reported to be caused by other genetic mutations that a¡ect transcription, 1 RNA processing, 2 RNA transport (nucleus to cytoplasm), 3 mRNA stability in the cytoplasm, 4 nonsense-mediated mRNA decay, 5 or a combination of these factors. In this study to examine the cause of the drastically reduced mutant mRNA level in the reticulocytes from a patient with a G4C splicing junction mutation in IVS1--1of the b-globin gene, 6 we analysed the mRNA encoded by the cloned mutant gene in COS-1 cells.…”

Avaliação dos parâmetros bioquímicos e hematológicos associados ao estudo molecular para caracterização da beta-talassemia heterozigótica

“…O promotor da β-globina, a exemplo de muitos outros promotores gênicos, consiste numa série de elementos funcionais relativamente curtos que se acredita interagirem com proteínas que regulam transcrição, incluindo, no caso dos genes da globina, as proteínas que controlam a expressão específica desses genes nas células eritróides, que compõem o tecido no qual a hemoglobina é produzida (11) . bases deletados e ocorrem geralmente nas regiões 3' e 5'-UTR da fita gênica da β-globina (30,31) . Atualmente, a maioria das β-talassemias é causada por mutações não -deletérias.…”