Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis

@article{Palmer2006CommonLV,
  title={Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis},
  author={Colin N. A. Palmer and Alan D. Irvine and Ana Terron-Kwiatkowski and Yiwei Zhao and Haihui Liao and Simon P. Lee and David R. Goudie and Aileen Sandilands and Linda E. Campbell and Frances J. D. Smith and Gr{\'a}inne M. O’Regan and Rosemarie M. Watson and Joanne E Cecil and Sherri J. Bale and John G. Compton and John J. DiGiovanna and Philip Fleckman and S. Lewis-jones and Gehan Arseculeratne and Ann Sergeant and Colin S. Munro and Brahim El Houate and Ken McElreavey and Liselotte Brydensholt Halkjaer and Hans Bisgaard and Somnath Mukhopadhyay and W.H. Irwin McLean},
  journal={Nature Genetics},
  year={2006},
  volume={38},
  pages={441-446}
}
Atopic disease, including atopic dermatitis (eczema), allergy and asthma, has increased in frequency in recent decades and now affects ∼20% of the population in the developed world. Twin and family studies have shown that predisposition to atopic disease is highly heritable. Although most genetic studies have focused on immunological mechanisms, a primary epithelial barrier defect has been anticipated. Filaggrin is a key protein that facilitates terminal differentiation of the epidermis and… 
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The Role of Filaggrin Mutations as an Etiologic Factor in Atopic Dermatitis
TLDR
It is shown that two independent loss-of-function genetic variants (R510X and 2282del4) in the gene encoding filaggrin (FLG) are very strong predisposing factors for atopic dermatitis, carried by 9% of people of European origin.
Loss-of-function variations within the filaggrin gene predispose for atopic dermatitis with allergic sensitizations.
Filaggrin gene defects and the risk of developing allergic disorders.
TLDR
The restoration of skin barrier function seems a feasible and promising strategy for prophylactic treatment of AD patients with FLG mutations, which are significantly associated with AD-associated asthma.
The role of filaggrin loss-of-function mutations in atopic dermatitis
TLDR
Focusing on the downstream biological consequences of altered filaggrin expression and the sequence of immunological and environmental triggers that ensue will provide the rationale for targeted therapeutics capable of restoring or preventing disruption of barrier function.
Review paper The role of filaggrin gene mutations in pathogenesis of atopic dermatitis. Literature review
TLDR
Recent studies revealed that null mutations in filaggrin genes that cause ichthyosis vulgaris are strong predisposing factors for atopic dermatitis and asthma, and the first study on the role of filag Grin mutations in AD was successfully replicated in the other populations.
Filaggrin loss-of-function mutations predispose to phenotypes involved in the atopic march.
Filaggrin mutations and atopy: consequences for future therapeutics
TLDR
The skin barrier disruptions of atopic eczema associated with loss-of-function mutations in filaggrin are thought to provide a nidus for allergic sensitization to food and aeroallergens, which can lead to increased allergic disease.
Filaggrin Loss-of-Function Mutations Are Risk Factors for Severe Food Allergy in Children with Atopic Dermatitis
TLDR
It is demonstrated that atopic children carrying FLG mutations represent a high-risk population due to their predisposition to develop severe food allergy reactions, such as anaphylaxis.
Loss-of-function mutations in the filaggrin gene and allergic contact sensitization to nickel.
TLDR
It is concluded that a genetically determined FLG deficiency manifests as dry skin and features of ichthyosis vulgaris, andFLG deficiency may also represent a risk factor for contact sensitization to allergens.
The role of a genetically impaired epidermal barrier as a major predisposing factor in the pathogenesis of atopic
  • Biology
  • 2007
TLDR
The association of atopic dermatitis with fil­ aggrin variants was confirmed, but not that of SPINK5 or KLK7 polymorphisms, and SCORAD and TEWL meas­ urements were not influenced by any of the variants.
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References

SHOWING 1-10 OF 36 REFERENCES
The genetics of atopic dermatitis.
Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis vulgaris
TLDR
It is found that loss or reduction of this major structural protein, filaggrin, leads to varying degrees of impaired keratinization.
Association of the ADAM33 gene with asthma and bronchial hyperresponsiveness
TLDR
The identification and characterization of ADAM33, a putative asthma susceptibility gene identified by positional cloning in an outbred population, should provide insights into the pathogenesis and natural history of this common disease.
Impaired sphingomyelinase activity and epidermal differentiation in atopic dermatitis.
TLDR
Reduction in SMase-generating ceramides and impaired differentiation are involved in the defective barrier function found in AD.
Decreased expression of filaggrin in atopic skin
TLDR
Evidence that only the expression of filaggrin was suppressed in AD patients, though the genes of filggrin and involucrin are localized to a very restricted portion of the same gene 1q21, indicates that the filag Grin gene does not share regulatory elements with the involucin gene.
Filaggrin repeat number polymorphism is associated with a dry skin phenotype
TLDR
Preliminary evidence of an inverse association between the 12 repeat allele and self-perceived frequent dry skin is identified and suggests that cosmetic skin dryness may in part be genetically determined and associated with specific profilaggrin allelotypes.
Atopic dermatitis and the atopic march.
The atopic eczema/dermatitis syndrome. Epidemiology, natural course, and immunology of the IgE-associated ("extrinsic") and the nonallergic ("intrinsic") AEDS.
TLDR
The so-called "intrinsic" type of AD (now termed nonallergic AEDS) fulfills the most commonly used diagnostic criteria for AD and is essential for the allergological management of patients as to allergen avoidance, secondary allergy prevention, and immunotherapy.
Mapping of the associated phenotype of an absent granular layer in ichthyosis vulgaris to the epidermal differentiation complex on chromosome 1 *
TLDR
The AGL may represent an endophenotype for IV, and the presence of a modifier of IV pathology at this locus is discussed.
The epidemiology of atopic dermatitis at a tertiary referral skin center in Singapore.
TLDR
The profile of atopic dermatitis seen at the National Skin Centre in Singapore is described, similar to that reported in the Western literature except for a lower prevalence and a significant proportion of adult onset atopy.
...
1
2
3
4
...