Factor VII gene intronic mutation in a lethal factor VII deficiency: effects on splice-site selection.
Blood
; 102(2): 561-3, 2003 Jul 15.
Article
em En
| MEDLINE
| ID: mdl-12676783
ABSTRACT
In a patient with lethal factor VII (FVII) deficiency, 2 homozygous nucleotide substitutions were identified in the F7 gene a IVS7+2T>G transversion involving the IVS7 donor splice site, followed by a mutation at nucleotide 10588 that would result in a missense variation (Arg224Gln). The mutated splice site, located within the first repeat of a minisatellite, is followed by a variable number of pseudo-sites, normally silent. To investigate the consequences of this mutation on F7 splicing, we designed normal and mutant minigenes, spanning exons 5 to 8. In cells transfected with the mutant construct, no normal splicing occurred. Only spliced transcripts including the first minisatellite repeat were observed, resulting from the activation of the most proximal wild-type pseudo-site, which would generate a truncated protein (stop codon upstream of nucleotide 10588). These findings, which suggest the existence of a mechanism selecting one single splice site among multiple cryptic sites, explain the patient's phenotype.
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Base de dados:
MEDLINE
Assunto principal:
Fator VII
/
Íntrons
/
Splicing de RNA
/
Sítios de Splice de RNA
/
Deficiência do Fator VII
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article