Characterization of new mutations in the 5'-flanking region of the familial Mediterranean fever gene.
Genes Immun
; 10(3): 273-9, 2009 Apr.
Article
em En
| MEDLINE
| ID: mdl-19262573
ABSTRACT
Familial Mediterranean fever (FMF) is a recessive autoinflammatory disease commonly found in the Mediterranean populations. Genetic diagnosis has developed since the discovery of the causative gene MEFV in 1997. As many patients could not be confirmed genetically by routine exon screening, we searched for mutations in the 5'-flanking region of this gene. Using denaturing gradient gel electrophoresis, we screened DNA from 108 patients with clinical FMF and 91 asymptomatic individuals. We found six novel sequence variants in a region extending -825 bp upstream of the first translated codon. To investigate the potential role of these variants in altering MEFV gene expression, we first characterized the MEFV promoter. Promoter mapping assays revealed that the region located between nucleotides -949 and -152 of the initiation codon was important for regulating expression of the gene. We identified a putative enhancer element between -571 and -414. Investigation of the sequence variants found in two patients demonstrated that c.-614C>G resulted in a 70% decrease in promoter activity, whereas c.-382C>T induced a 100% increase in activity, when compared to the wild type. We observed specific DNA-protein binding to both wild-type sites, suggesting that transcription factors may bind to these sequences to modulate MEFV expression.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Febre Familiar do Mediterrâneo
/
Predisposição Genética para Doença
/
Proteínas do Citoesqueleto
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
Genes Immun
Assunto da revista:
ALERGIA E IMUNOLOGIA
/
BIOLOGIA MOLECULAR
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
França