Beta+45 G --> C: a novel silent beta-thalassaemia mutation, the first in the Kozak sequence
| Autoři: | De Angioletti M., Lacerra G., Sabato V., Carestia C. |
|---|---|
| Zdroj: | British journal of haematology 124 (2004): 224–231. doi:10.1046/j.1365-2141.2003.04754.x info:cnr-pdr/source/autori:De Angioletti M.; Lacerra G.; Sabato V.; Carestia C./titolo:Beta+45 G--> C: a novel silent beta-thalassaemia mutation, the first in the Kozak sequence/doi:10.1046%2Fj.1365-2141.2003.04754.x/rivista:British journal of haematology (Print)/anno:2004/pagina_da:224/pagina_a:231/intervallo_pagine:224–231/volume:124 |
| Informace o vydavateli: | Blackwell, Oxford , Regno Unito, 2004. |
| Rok vydání: | 2004 |
| Témata: | silent beta-thalassaemia, Kozak consensus sequence, leader sequence, beta-thalassaemia modifier |
| Popis: | A family from the Southeast of Italy was found to have a novel beta-globin mutant, beta+45 G ->C, with the features of a silent beta-thalassaemia mutation. It was asymptomatic in two heterozygotes, but its interaction with the severe thalassaemia mutation beta-IVS-II-654 C->T worsened the haematological and biosynthetic phenotype in two compound heterozygotes; moreover, another compound heterozygote, who was also heterozygote for the aaa anti3.7, suffered from thalassaemia intermedia. The mutation was found associated in cis with the IVS-II-754 T->C substitution, which did not lead to abnormally spliced mRNA. Furthermore, the amount of beta+45 mRNA was the same as the beta A mRNA in the reticulocytes of the carriers. In vitro transcription/translation experiments demonstrated that the beta+45 G->C decreased the efficiency of translation of the beta-globin chain by about 30%: this slight impairment was consistent with the observed clinical phenotype. The beta+45 G->C is the first mutation found in the Kozak sequence (GACACCATGG) of the beta-globin gene and the first one at the position -6 upstream the ATG. The Kozak consensus sequence plays a major role in the initiation of translation process. The present finding supports the hypothesis that the G in position -6 is important in this process. |
| Jazyk: | English |
| DOI: | 10.1046/j.1365-2141.2003.04754.x |
| Přístupová URL adresa: | https://explore.openaire.eu/search/publication?articleId=cnr_________::bd756f6fe7ca4352e9b8d0314893d780 http://www.cnr.it/prodotto/i/26650 |
| Rights: | CLOSED |
| Přírůstkové číslo: | edsair.cnr...........bd756f6fe7ca4352e9b8d0314893d780 |
| Autor: | De Angioletti M., Lacerra G., Sabato V., Carestia C. |
| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: | |
| Zdroj: | British journal of haematology 124 (2004): 224–231. doi:10.1046/j.1365-2141.2003.04754.x info:cnr-pdr/source/autori:De Angioletti M.; Lacerra G.; Sabato V.; Carestia C./titolo:Beta+45 G--> C: a novel silent beta-thalassaemia mutation, the first in the Kozak sequence/doi:10.1046%2Fj.1365-2141.2003.04754.x/rivista:British journal of haematology (Print)/anno:2004/pagina_da:224/pagina_a:231/intervallo_pagine:224–231/volume:124 |
| DOI: | 10.1046/j.1365-2141.2003.04754.x |
| Popis: | A family from the Southeast of Italy was found to have a novel beta-globin mutant, beta+45 G ->C, with the features of a silent beta-thalassaemia mutation. It was asymptomatic in two heterozygotes, but its interaction with the severe thalassaemia mutation beta-IVS-II-654 C->T worsened the haematological and biosynthetic phenotype in two compound heterozygotes; moreover, another compound heterozygote, who was also heterozygote for the aaa anti3.7, suffered from thalassaemia intermedia. The mutation was found associated in cis with the IVS-II-754 T->C substitution, which did not lead to abnormally spliced mRNA. Furthermore, the amount of beta+45 mRNA was the same as the beta A mRNA in the reticulocytes of the carriers. In vitro transcription/translation experiments demonstrated that the beta+45 G->C decreased the efficiency of translation of the beta-globin chain by about 30%: this slight impairment was consistent with the observed clinical phenotype. The beta+45 G->C is the first mutation found in the Kozak sequence (GACACCATGG) of the beta-globin gene and the first one at the position -6 upstream the ATG. The Kozak consensus sequence plays a major role in the initiation of translation process. The present finding supports the hypothesis that the G in position -6 is important in this process. |
| Databáze: | OpenAIRE |
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