Comprehensive analysis of the gene encoding filaggrin uncovers prevalent and rare mutations in ichthyosis vulgaris and atopic eczema.
Nat Genet
; 39(5): 650-4, 2007 May.
Article
em En
| MEDLINE
| ID: mdl-17417636
ABSTRACT
We recently reported two common filaggrin (FLG) null mutations that cause ichthyosis vulgaris and predispose to eczema and secondary allergic diseases. We show here that these common European mutations are ancestral variants carried on conserved haplotypes. To facilitate comprehensive analysis of other populations, we report a strategy for full sequencing of this large, highly repetitive gene, and we describe 15 variants, including seven that are prevalent. All the variants are either nonsense or frameshift mutations that, in representative cases, resulted in loss of filaggrin production in the epidermis. In an Irish case-control study, the five most common European mutations showed a strong association with moderate-to-severe childhood eczema (chi2 test P = 2.12 x 10(-51); Fisher's exact test heterozygote odds ratio (OR) = 7.44 (95% confidence interval (c.i.) = 4.9-11.3), and homozygote OR = 151 (95% c.i. = 20-1,136)). We found three additional rare null mutations in this case series, suggesting that the genetic architecture of filaggrin-related atopic dermatitis consists of both prevalent and rare risk alleles.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ictiose Vulgar
/
Predisposição Genética para Doença
/
Dermatite Atópica
/
Proteínas de Filamentos Intermediários
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Humans
País/Região como assunto:
Europa
Idioma:
En
Revista:
Nat Genet
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Reino Unido