Factors modulating the effects of filaggrin haploinsufficiency in ichthyosis vulgaris and atopic eczema. (360G-Wellcome-086398_Z_08_Z)

£560,441

Null mutations in the filaggrin gene (FLG) cause ichthyosis vulgaris and are significantly associated with atopic eczema. FLG null mutations are prevalent in the European population, with a combined allele frequency of 0.09. However, the penetrance has been estimated at between 42% and 79% in atopic eczema, demonstrating the importance of factors modulating the effects of filaggrin haploinsufficiency in skin disease. This project aims to test three hypotheses: (1) Copy number variation bot h within and around the FLG locus modulates penetrance. Assays to detect copy number variants will be developed and applied to the study of established cohorts of children with eczema. (2) FLG expression demonstrates positive and negative interactions with other genes involved in epidermal barrier function. This will be investigated using microarray technology and findings corroborated with quantitative PCR and immunoblotting. (3) FLG null mutations result in a reduced amount of epi dermal histidine, which affects response to UVB therapy. The response of eczema patients to phototherapy will be correlated with FLG null status in a retrospective pilot study, followed by a more detailed prospective study. The proposed research will improve understanding of the mechanisms by which FLG null mutations and filaggrin deficiency contribute to the pathogenesis of eczema.

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Grant Details

Amount Awarded 560441
Applicant Surname Brown
Approval Committee Clinical Interview Committee
Award Date 2008-12-04T00:00:00+00:00
Financial Year 2008/09
Grant Programme: Title Intermediate Clinical Fellowship
Internal ID 086398/Z/08/Z
Lead Applicant Prof Sara Brown
Partnership Value 560441
Planned Dates: End Date 2015-06-30T00:00:00+00:00
Planned Dates: Start Date 2009-07-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Scotland
Sponsor(s) Prof Irene Leigh, Prof Irwin McLean