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PloS One 2013To explore the usefulness of protein profiling for characterization of ichthyoses, we here determined the profile of human epidermal stratum corneum by shotgun...
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.
Topics: Adolescent; Adult; Aged; Connexin 26; Connexins; Female; Filaggrin Proteins; Gene Expression Profiling; Humans; Ichthyosis; Ichthyosis Vulgaris; Male; Middle Aged; Mutation; Steryl-Sulfatase; Transglutaminases; Young Adult
PubMed: 24130705
DOI: 10.1371/journal.pone.0075355 -
Canadian Family Physician Medecin de... Dec 1998
Topics: Administration, Topical; Adult; Antipruritics; Baths; Child; Diagnosis, Differential; Emollients; Humans; Ichthyosis Vulgaris; Keratolytic Agents; Lactic Acid; Male; Propionates; Quaternary Ammonium Compounds; Salicylic Acid
PubMed: 9870115
DOI: No ID Found -
Indian Journal of Dermatology 2021
PubMed: 34188288
DOI: 10.4103/ijd.IJD_125_20 -
Ugeskrift For Laeger Jul 2014A new classification of inherited ichthyoses is presented based on clinical features, genetic background and pathophysiology. Ichthyoses are disorders of cornification... (Review)
Review
A new classification of inherited ichthyoses is presented based on clinical features, genetic background and pathophysiology. Ichthyoses are disorders of cornification and may be part of syndromes. Ichthyosis vulgaris, X-linked ichthyosis, autosomal recessive congenital ichthyosis and syndrome-related variants are described. Severe forms can be potentially life-threatening. Dry scaly skin can be disabling and time-consuming, as the patient needs topical therapy and sometimes also systemic retinoids. Treatment today is symptomatic, but hopefully new knowledge will lead to targeted therapies.
Topics: Dermatologic Agents; Genetic Predisposition to Disease; Humans; Ichthyosis; Skin
PubMed: 25292205
DOI: No ID Found -
Genes Mar 2021Ichthyoses are a large group of hereditary cornification disorders, which are both clinically and etiologically heterogeneous and affect mostly all the skin surface of...
BACKGROUND
Ichthyoses are a large group of hereditary cornification disorders, which are both clinically and etiologically heterogeneous and affect mostly all the skin surface of the patients. Ichthyosis has its origin in an ancient Greek word "ichthys" meaning fish, this is because the ichthyosis patients have dry, thickened, and scaly skin. There is an excess accumulation of epidermal cells resulting in the appearance of continuous and widespread scales on the body. There are many varieties of ichthyosis with a broad spectrum of intensity, severity, and associated symptoms, most of them are extremely rare. Ichthyosis vulgaris is the most frequently occurring type of ichthyoses.
METHOD
The present study consists of four Pakistani ichthyosis families (A, B, C, and D). Whole exome sequencing (WES) approach was used to identify the pathogenic sequence variants in probands. The segregation of these variants in other participants was confirmed by Sanger sequencing.
RESULTS
Total four variants including, two splice site (: c.2088 + 1G > A) and (: c.882 + 1G > T), a missense (: c.419C > T; p. Ala140Val), and a nonsense (: c.6109C > T; p. Arg2037Ter) variant were identified in families A, C, B, and D, respectively, as causative mutations responsible for ichthyosis in these families.
CONCLUSION
Our study unravels the molecular etiology of the four Pakistani ichthyosis families and validates the involvement of and , in the etiology of different forms of ichthyosis. In addition, this study also aims to give a detailed clinical report of the studied ichthyosis families.
Topics: Adult; Case-Control Studies; Child; Consanguinity; Female; Filaggrin Proteins; Genetic Predisposition to Disease; Homozygote; Humans; Ichthyosis; Male; Mutation; Pakistan; Pedigree; Phenotype; S100 Proteins; Serine Peptidase Inhibitor Kazal-Type 5; Sulfotransferases; Transglutaminases; Exome Sequencing
PubMed: 33807935
DOI: 10.3390/genes12030373 -
The Journal of Investigative Dermatology Feb 2009The eczemas represent a common and diverse group of inflammatory skin diseases whose definitions and pathogenic mechanisms have often been confused and controversial.... (Review)
Review
The eczemas represent a common and diverse group of inflammatory skin diseases whose definitions and pathogenic mechanisms have often been confused and controversial. Since the millennium, fresh approaches are providing better insight. Research has focused much more upon the epidermis and the very relevant signaling pathways that contribute to spongiosis, proliferation, generation of proinflammatory factors, and differentiation to form an effective stratum corneum barrier. A major step in understanding has come from the solidly confirmed association between filaggrin null mutations of ichthyosis vulgaris and atopic dermatitis. Similar associations relating to protease and lipid defects have highlighted the role of barrier disruption that allows greater access of environmental toxins, microbes, and allergens. Animal models are beginning to predict mechanisms in which such direct perturbation of keratinocytes may initiate inflammation and condition immune responses in irritant contact dermatitis and atopic dermatitis. These conceptual shifts are nurturing more balanced approaches to understanding eczema and hold the hope for better prevention efforts and more specific molecular targeting for therapy.
Topics: Animals; Dermatitis, Atopic; Eczema; Filaggrin Proteins; Humans; Keratinocytes; Signal Transduction
PubMed: 18719604
DOI: 10.1038/jid.2008.252 -
BMC Medical Genomics Oct 2023Ichthyoses are a heterogeneous group of cornification disorders. The most common form of ichthyoses is ichthyosis vulgaris (IV) ([OMIM] #146,700), which can be inherited...
Ichthyoses are a heterogeneous group of cornification disorders. The most common form of ichthyoses is ichthyosis vulgaris (IV) ([OMIM] #146,700), which can be inherited as autosomal semi-dominant mutation in the filaggrin gene (FLG). We present the findings of a study involving 35 Saudi patients with a clinical diagnosis of ichthyosis vulgaris. For identifying the pathogenic mutation of their disease, we used Sanger sequencing analysis of the extracted DNA samples. We also identified the underlying 22 FLG variants, which have been seen before. However, the detected mutations do not involve the common p.R501* c. 2282del4 mutations reported in European populations. Indeed, we did not identify any statistical influence of the homozygous or heterozygous genotypes on the phenotype severity of the disease.
Topics: Humans; Dermatitis, Atopic; Filaggrin Proteins; Genetic Predisposition to Disease; Ichthyosis Vulgaris; Intermediate Filament Proteins; Mutation; Saudi Arabia
PubMed: 37872553
DOI: 10.1186/s12920-023-01700-x -
Clinical Case Reports Sep 2023Coexistence of TGM1 and FLG mutations in a newborn with congenital ichthyosis is not well described in the literature. Early genetic testing and counseling are crucial...
Coexistence of TGM1 and FLG mutations in a newborn with congenital ichthyosis is not well described in the literature. Early genetic testing and counseling are crucial for accurate diagnosis and appropriate management. Further exploration of associated problems, including hearing loss and developmental delay, is warranted in patients with these mutations.
PubMed: 37736478
DOI: 10.1002/ccr3.7910 -
The Journal of Investigative Dermatology Jan 2021Atopic dermatitis (AD) is an inflammatory skin disease in which epidermal barrier impairment, often owing to FLG null mutations, precedes immune hyperresponsiveness....
Atopic dermatitis (AD) is an inflammatory skin disease in which epidermal barrier impairment, often owing to FLG null mutations, precedes immune hyperresponsiveness. Ichthyosis vulgaris is characterized by FLG null mutations and noninflamed dry skin. Netherton syndrome (NS), caused by SPINK5 null mutations, is characterized by generalized erythroderma with scaling and atopic manifestations. The goal of this work was to evaluate associations between specific skin disease features, such as ichthyotic and/or atopic manifestations, and the skin bacterial and fungal microbiota. Taxon diversity showed greater variation in the bacterial microbiota than in the fungal microbiota in the skin diseases. The relative abundances of Firmicutes (Staphylococcus) and Actinobacteria (Corynebacterium) were augmented in ichthyosis vulgaris, AD, and NS, whereas those of Proteobacteria/Enhydrobacter and Bacteroidetes were reduced, regardless of body site. Furthermore, proportions of Staphylococcus were correlated with transepidermal water loss and serum IgE levels. Nevertheless, the skin of patients with low to mild AD was overcolonized with Staphylococcus epidermidis and not with Staphylococcus aureus. Ascomycota were increased in both AD and NS, but from expansion of different fungal species. Finally, the expansion of pathologic bacteria in AD and NS might be supported by surrounding fungi. Thus, distinguishable bacterial and fungal skin dysbiosis in AD, NS, and ichthyosis vulgaris emphasizes disease-specific pathomechanisms.
Topics: Adult; Bacteria; Dermatitis, Atopic; Dysbiosis; Female; Filaggrin Proteins; Fungi; Humans; Male; Microbiota; Netherton Syndrome; Skin
PubMed: 32553662
DOI: 10.1016/j.jid.2020.05.102 -
The Journal of Investigative Dermatology Sep 2017AP1 transcription factors are important controllers of gene expression in the epidermis, and altered AP1 factor function can perturb keratinocyte proliferation and...
AP1 transcription factors are important controllers of gene expression in the epidermis, and altered AP1 factor function can perturb keratinocyte proliferation and differentiation. However, our understanding of how AP1 signaling changes may underlie or exacerbate skin disease is limited. We have shown that inhibiting AP1 factor function in suprabasal adult epidermis leads to reduced filaggrin levels and to a phenotype that resembles the genetic disorder ichthyosis vulgaris. We now show that inhibiting AP1 factor function during development in embryonic epidermis produces marked phenotypic changes including reduced filaggrin mRNA and protein levels, compromised barrier function, marked ultrastructural change, and enhanced dehydration susceptibility that resembles the phenotype observed in the flaky tail mouse, a model for ichthyosis vulgaris. In addition, the AP1 factor-deficient newborn mice display a collodion membrane phenotype that is not observed in flaky tail mice or in newborn individuals with ichthyosis vulgaris but is present in other forms of ichthyosis. This mixed phenotype suggests the need for a better understanding of the possible role of filaggrin loss and AP1 transcription factor deficiency in ichthyoses and collodion membrane formation.
Topics: Animals; Animals, Newborn; Biopsy, Needle; Cell Differentiation; Cells, Cultured; Disease Models, Animal; Filaggrin Proteins; Humans; Ichthyosiform Erythroderma, Congenital; Immunohistochemistry; Intermediate Filament Proteins; Keratinocytes; Mice; Mice, Transgenic; Phenotype; Random Allocation; Sensitivity and Specificity; Signal Transduction; Transcription Factor AP-1
PubMed: 28526300
DOI: 10.1016/j.jid.2017.04.032