Exacerbation of X-linked ichthyosis phenotype in a female by inheritance of filaggrin and steroid sulfatase mutations

Ramesh, Raakhee; Chen, Huijia; Kukuła, Anna; Wakeling, Emma; Rustin, M.H.A.; McLean, W.H. Irwin

doi:10.1016/j.jdermsci.2011.07.006

Cited by 24 publications

(18 citation statements)

References 19 publications

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“…Yet, in the absence of an X-linked pedigree, phenotypic overlap with other mild-to-moderate ichthyosis requires further studies to definitively establish the diagnosis of XLI. Moreover, because IV and the xerosis associated with atopic dermatitis (AD) are both quite common, the two disorders may co-exist, producing a more severe phenotype in affected patients [10–12]. Indeed, both of these disorders are relatively-common (XLI occurs in 1:1,800; filaggrin mutations occur in up to 10% of the European population).…”

Section: Clinical Featuresmentioning

confidence: 99%

Role of cholesterol sulfate in epidermal structure and function: Lessons from X-linked ichthyosis

Elias

Williams

Choi

et al. 2014

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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X-linked ichthyosis is a relatively common syndromic form of ichthyosis most often due to deletions in the gene encoding the microsomal enzyme, steroid sulfatase, located on the short area of the X chromosome. Syndromic features are mild or unapparent unless contiguous genes are affected. In normal epidermis, cholesterol sulfate is generated by cholesterol sulfotransferase (SULT2B1b), but desulfated in the outer epidermis, together forming a ‘cholesterol sulfate cycle’ that potently regulates epidermal differentiation, barrier function and desquamation. In XLI, cholesterol sulfate levels my exceed 10% of total lipid mass (≈1% of total weight). Multiple cellular and biochemical processes contribute to the pathogenesis of the barrier abnormality and scaling phenotype in XLI. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias.

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Section: Clinical Featuresmentioning

confidence: 99%

Role of cholesterol sulfate in epidermal structure and function: Lessons from X-linked ichthyosis

Elias

Williams

Choi

et al. 2014

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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“…Abnormal barrier function in IV drives compensatory repair mechanisms that include epidermal hyperplasia, resulting in hyperkeratosis. A synergetic effect of mutations in FLG and the steroid sulfatase gene leading to more severe ichthyosis has been reported in patients with IV and X‐linked ichthyosis 39 . Because of the lower levels of filaggrin proteins, individuals with IV have reduced epidermal chromophore UCA levels, 27,40,41 and knockdown of filaggrin increased UV sensitivity markedly in vitro 42 .…”

Section: Filaggrin’s Role In the Skin Barriermentioning

confidence: 99%

Ichthyosis vulgaris: the filaggrin mutation disease

Thyssen

Godoy-Gijón

Elias

2013

British Journal of Dermatology

133

131

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Ichthyosis vulgaris is caused by loss-of-function mutations in the filaggrin gene (FLG) and is characterized clinically by xerosis, scaling, keratosis pilaris, palmar and plantar hyperlinearity, and a strong association with atopic disorders. According to the published studies presented in this review article, FLG mutations are observed in approximately 7·7% of Europeans and 3·0% of Asians, but appear to be infrequent in darker-skinned populations. This clinical review article provides an overview of ichthyosis vulgaris epidemiology, related disorders and pathomechanisms. Not only does ichthyosis vulgaris possess a wide clinical spectrum, recent studies suggest that carriers of FLG mutations may have a generally altered risk of developing common diseases, even beyond atopic disorders. Mechanistic studies have shown increased penetration of allergens and chemicals in filaggrin-deficient skin, and epidemiological studies have found higher levels of hand eczema, irritant contact dermatitis, nickel sensitization and serum vitamin D levels. When relevant, individuals should be informed about an increased risk of developing dermatitis when repeatedly or continuously exposed to nickel or irritants. Moreover, with our current knowledge, individuals with ichthyosis vulgaris should be protected against neonatal exposure to cats to prevent atopic dermatitis and should abstain from smoking to prevent asthma. Finally, they should be advised against excessive exposure to factors that decrease skin barrier functions and increase the risk of atopic dermatitis.

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“…In some instances, the severity is influenced by the coincidence of more than a single predisposing gene defect. For example, X-linked ichthyosis (XLI) can be exacerbated by a concomitant FLG mutation acting as a modifier [17]; however, other yet unknown genes could also modify the phenotype [18].…”

Section: Introductionmentioning

confidence: 99%

Distinguishing Ichthyoses by Protein Profiling

et al. 2013

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To explore the usefulness of protein profiling for characterization of ichthyoses, we here determined the profile of human epidermal stratum corneum by shotgun proteomics. Samples were analyzed after collection on tape circles from six anatomic sites (forearm, palm, lower leg, forehead, abdomen, upper back), demonstrating site-specific differences in profiles. Additional samples were collected from the forearms of subjects with ichthyosis vulgaris (filaggrin (FLG) deficiency), recessive X-linked ichthyosis (steroid sulfatase (STS) deficiency) and autosomal recessive congenital ichthyosis type lamellar ichthyosis (transglutaminase 1 (TGM1) deficiency). The ichthyosis protein expression patterns were readily distinguishable from each other and from phenotypically normal epidermis. In general, the degree of departure from normal was lower from ichthyosis vulgaris than from lamellar ichthyosis, parallel to the severity of the phenotype. Analysis of samples from families with ichthyosis vulgaris and concomitant modifying gene mutations (STS deficiency, GJB2 deficiency) permitted correlation of alterations in protein profile with more complex genetic constellations.

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Exacerbation of X-linked ichthyosis phenotype in a female by inheritance of filaggrin and steroid sulfatase mutations

Cited by 24 publications

References 19 publications

Role of cholesterol sulfate in epidermal structure and function: Lessons from X-linked ichthyosis

Role of cholesterol sulfate in epidermal structure and function: Lessons from X-linked ichthyosis

Ichthyosis vulgaris: the filaggrin mutation disease

Distinguishing Ichthyoses by Protein Profiling

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