Dataset Information

Filaggrin genotype in ichthyosis vulgaris predicts abnormalities in epidermal structure and function.

ABSTRACT: Although it is widely accepted that filaggrin (FLG) deficiency contributes to an abnormal barrier function in ichthyosis vulgaris and atopic dermatitis, the pathomechanism of how FLG deficiency provokes a barrier abnormality in humans is unknown. We report here that the presence of FLG mutations in Caucasians predicts dose-dependent alterations in epidermal permeability barrier function. Although FLG is an intracellular protein, the barrier abnormality occurred solely via a paracellular route in affected stratum corneum. Abnormal barrier function correlated with alterations in keratin filament organization (perinuclear retraction), impaired loading of lamellar body contents, followed by nonuniform extracellular distribution of secreted organelle contents, and abnormalities in lamellar bilayer architecture. In addition, we observed reductions in corneodesmosome density and tight junction protein expression. Thus, FLG deficiency provokes alterations in keratinocyte architecture that influence epidermal functions localizing to the extracellular matrix. These results clarify how FLG mutations impair epidermal permeability barrier function.

SUBMITTER: Gruber R

PROVIDER: S-EPMC3081164 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Filaggrin genotype in ichthyosis vulgaris predicts abnormalities in epidermal structure and function.

Gruber Robert R Elias Peter M PM Crumrine Debra D Lin Tzu-Kai TK Brandner Johanna M JM Hachem Jean-Pierre JP Presland Richard B RB Fleckman Philip P Janecke Andreas R AR Sandilands Aileen A McLean W H Irwin WH Fritsch Peter O PO Mildner Michael M Tschachler Erwin E Schmuth Matthias M

The American journal of pathology 20110501 5

Although it is widely accepted that filaggrin (FLG) deficiency contributes to an abnormal barrier function in ichthyosis vulgaris and atopic dermatitis, the pathomechanism of how FLG deficiency provokes a barrier abnormality in humans is unknown. We report here that the presence of FLG mutations in Caucasians predicts dose-dependent alterations in epidermal permeability barrier function. Although FLG is an intracellular protein, the barrier abnormality occurred solely via a paracellular route in ...[more]

PMID: 21514438

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Project description:BackgroundHigh rates of adverse mood/neurodevelopmental traits are seen in multiple dermatological conditions, and can significantly affect patient quality of life. Understanding the sex-specific nature, magnitude, impact and basis of such traits in lesser-studied conditions like ichthyosis, is important for developing effective interventions.AimTo quantify and compare relevant psychological traits in men with X-linked ichthyosis (XLI, n = 54) or in XLI carrier women (n = 83) and in patients with ichthyosis vulgaris (IV, men n = 23, women n = 59) or psoriasis (men n = 30, women n = 122), and to identify factors self-reported to contribute most towards depressive, anxious and irritable phenotypes.MethodsParticipants recruited via relevant charities or social media completed an online survey of established questionnaires. Data were analysed by sex and skin condition, and compared with general population data.ResultsCompared with the general population, there was a higher rate of lifetime prevalence of mood disorder diagnoses across all groups and of neurodevelopmental disorder diagnoses in the XLI groups. The groups exhibited similarly significant elevations in recent mood symptoms (Cohen d statistic 0.95-1.28, P < 0.001) and neurodevelopmental traits (d = 0.31-0.91, P < 0.05) compared with general population controls, and self-reported moderate effects on quality of life and stigmatization. There were strong positive associations between neurodevelopmental traits and recent mood symptoms (r > 0.47, P < 0.01), and between feelings of stigmatization and quality of life, particularly in men. Numerous factors were identified as contributing significantly to mood symptoms in a condition or sex-specific, or condition or sex-independent, manner.ConclusionWe found that individuals with XLI, IV or psoriasis show higher levels of mood disorder diagnoses and symptoms than matched general population controls, and that the prevalence and severity of these is similar across conditions. We also identified a number of factors potentially conferring either general or condition-specific risk of adverse mood symptoms in the three skin conditions, which could be targeted clinically and/or through education programmes. In clinical practice, recognizing mood/neurodevelopmental problems in ichthyosis and psoriasis, and addressing the predisposing factors identified by this study should benefit the mental health of affected individuals.

Dataset Information

Filaggrin genotype in ichthyosis vulgaris predicts abnormalities in epidermal structure and function.

Publications

Filaggrin genotype in ichthyosis vulgaris predicts abnormalities in epidermal structure and function.

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