The Experts below are selected from a list of 246 Experts worldwide ranked by ideXlab platform
W Irwin H Mclean - One of the best experts on this subject based on the ideXlab platform.
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a new filaggrin gene mutation in a korean patient with Ichthyosis vulgaris
European Journal of Dermatology, 2014Co-Authors: Yuka Ohguchi, Aileen Sandilands, Toshifumi Nomura, Shotaro Suzuki, Osamu Mizuno, Yukiko Nomura, Ikue Nemotohasebe, Hiroyuki Okamoto, Masashi Akiyama, W Irwin H McleanAbstract:Ichthyosis vulgaris (IV; OMIM 146700) is the most common genetic disorder of keratinization, inherited in an autosomal semi-dominant fashion, with incomplete penetrance [1]. IV is clinically characterized by dry skin and scaling, especially on the flexor limbs and the trunk [1]. Palmoplantar hyperlinearity and keratosis pilaris are also mostly associated. Loss-of-function mutations in the gene encoding filaggrin (FLG), a crucial protein for epidermal barrier function, have been identified as a cause [...]
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filaggrin genotype in Ichthyosis vulgaris predicts abnormalities in epidermal structure and function
American Journal of Pathology, 2011Co-Authors: Robert Gruber, Peter M Elias, Richard B Presland, Philip Fleckman, Aileen Sandilands, Debra Crumrine, Johanna M Brandner, Jean Pierre Hachem, Andreas R Janecke, W Irwin H McleanAbstract: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.
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unique and recurrent mutations in the filaggrin gene in singaporean chinese patients with Ichthyosis vulgaris
Journal of Investigative Dermatology, 2008Co-Authors: Aileen Sandilands, Alan Evans, Huijia Chen, Jean C C Ho, Yuin Chew Chan, Yoke Chin Giam, Birgitte E Lane, W Irwin H McleanAbstract:Filaggrin is an abundant protein of the outer epidermis that is essential for terminal differentiation of keratinocytes and formation of an effective barrier against water loss and pathogen/allergen/irritant invasion. Recent investigations in Europe and Japan have revealed null mutations in the filaggrin gene (FLG) as the underlying cause of Ichthyosis vulgaris (IV), a common skin disorder characterised by dry skin, palmar hyperlinearity and keratosis pilaris. Following the development of a strategy for the comprehensive analysis of FLG, we have identified five unique mutations and one recurrent mutation in Singaporean Chinese IV patients. Mutation 441delA is located in the profilaggrin S100 domain, whereas two additional frameshift mutations, 1249insG and 7945delA, occur in the first partial filaggrin repeat ("repeat 0") and in filaggrin repeat 7, respectively. Both nonsense mutations Q2147X and E2422X are found in filaggrin repeat 6, whereas R4307X was found on one of the longer size variant alleles of FLG, within duplicated repeat 10.2. Mutation E2422X, previously found in a single Dutch patient, was found in one Singaporean IV patient and at a low frequency in Asian population controls. Our study confirms the presence of population-specific as well as recurrent FLG mutations in Singapore.
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prevalent and rare mutations in the gene encoding filaggrin cause Ichthyosis vulgaris and predispose individuals to atopic dermatitis
Journal of Investigative Dermatology, 2006Co-Authors: Aileen Sandilands, Frances J D Smith, Ana Terronkwiatkowski, Yiwei Zhao, Haihui Liao, David Goudie, Rosemarie Watson, Grainne M Oregan, Andrew J Cassidy, W Irwin H McleanAbstract:Mutations in the filament aggregating protein (filaggrin) gene have recently been identified as the cause of the common genetic skin disorder Ichthyosis vulgaris (IV), the most prevalent inherited disorder of keratinization. The main characteristics of IV are fine-scale on the arms and legs, palmar hyperlinearity, and keratosis pilaris. Here, we have studied six Irish families with IV for mutations in filaggrin. We have identified a new mutation, 3702delG, in addition to further instances of the reported mutations R501X and 2282del4, which are common in people of European origin. A case of a 2282del4 homozygote was also identified. Mutation 3702delG terminates protein translation in filaggrin repeat domain 3, whereas both recurrent mutations occur in repeat 1. These mutations are semidominant: heterozygotes have an intermediate phenotype most readily identified by palmar hyperlinearity and in some cases fine-scale and/or keratosis pilaris, whereas homozygotes or compound heterozygotes generally have more marked Ichthyosis. Interestingly, the phenotypes of individuals homozygous for R501X, 2282del4, or compound heterozygous for R501X and 3702delG, were comparable, suggesting that mutations located centrally in the filaggrin repeats are also pathogenic.
Aileen Sandilands - One of the best experts on this subject based on the ideXlab platform.
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a new filaggrin gene mutation in a korean patient with Ichthyosis vulgaris
European Journal of Dermatology, 2014Co-Authors: Yuka Ohguchi, Aileen Sandilands, Toshifumi Nomura, Shotaro Suzuki, Osamu Mizuno, Yukiko Nomura, Ikue Nemotohasebe, Hiroyuki Okamoto, Masashi Akiyama, W Irwin H McleanAbstract:Ichthyosis vulgaris (IV; OMIM 146700) is the most common genetic disorder of keratinization, inherited in an autosomal semi-dominant fashion, with incomplete penetrance [1]. IV is clinically characterized by dry skin and scaling, especially on the flexor limbs and the trunk [1]. Palmoplantar hyperlinearity and keratosis pilaris are also mostly associated. Loss-of-function mutations in the gene encoding filaggrin (FLG), a crucial protein for epidermal barrier function, have been identified as a cause [...]
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filaggrin genotype in Ichthyosis vulgaris predicts abnormalities in epidermal structure and function
American Journal of Pathology, 2011Co-Authors: Robert Gruber, Peter M Elias, Richard B Presland, Philip Fleckman, Aileen Sandilands, Debra Crumrine, Johanna M Brandner, Jean Pierre Hachem, Andreas R Janecke, W Irwin H McleanAbstract: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.
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unique and recurrent mutations in the filaggrin gene in singaporean chinese patients with Ichthyosis vulgaris
Journal of Investigative Dermatology, 2008Co-Authors: Aileen Sandilands, Alan Evans, Huijia Chen, Jean C C Ho, Yuin Chew Chan, Yoke Chin Giam, Birgitte E Lane, W Irwin H McleanAbstract:Filaggrin is an abundant protein of the outer epidermis that is essential for terminal differentiation of keratinocytes and formation of an effective barrier against water loss and pathogen/allergen/irritant invasion. Recent investigations in Europe and Japan have revealed null mutations in the filaggrin gene (FLG) as the underlying cause of Ichthyosis vulgaris (IV), a common skin disorder characterised by dry skin, palmar hyperlinearity and keratosis pilaris. Following the development of a strategy for the comprehensive analysis of FLG, we have identified five unique mutations and one recurrent mutation in Singaporean Chinese IV patients. Mutation 441delA is located in the profilaggrin S100 domain, whereas two additional frameshift mutations, 1249insG and 7945delA, occur in the first partial filaggrin repeat ("repeat 0") and in filaggrin repeat 7, respectively. Both nonsense mutations Q2147X and E2422X are found in filaggrin repeat 6, whereas R4307X was found on one of the longer size variant alleles of FLG, within duplicated repeat 10.2. Mutation E2422X, previously found in a single Dutch patient, was found in one Singaporean IV patient and at a low frequency in Asian population controls. Our study confirms the presence of population-specific as well as recurrent FLG mutations in Singapore.
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specific filaggrin mutations cause Ichthyosis vulgaris and are significantly associated with atopic dermatitis in japan
Journal of Investigative Dermatology, 2008Co-Authors: Toshifumi Nomura, Aileen Sandilands, Alan Evans, Ikue Nemotohasebe, Masashi Akiyama, Kaori Sakai, Akari Nagasaki, Hiroo Hata, Colin N A Palmer, Hiroshi ShimizuAbstract:Mutations in the gene encoding filaggrin (FLG) have been identified as the cause of Ichthyosis vulgaris (IV) and shown to be major predisposing factors for atopic dermatitis (AD). However, these studies have been mainly carried out in European populations. In early 2007, we identified two Oriental-specific FLG mutations in four Japanese families with IV and reported that filaggrin mutations were also significant predisposing factors for AD in Japan. However, the frequency of FLG mutations observed in our Japanese AD cohort (5.6%), was much lower than that seen in Europeans (up to 48%). Here, we studied a further seven Japanese families with IV and identified two additional nonsense mutations in FLG, S2889X, and S3296X. We found that more than 20% of patients in our Japanese AD case series carry FLG mutations, and there is significant statistical association between the four mutations and AD (χ2 P=8.4 × 10−6; heterozygote odds ratio 7.57, 95% CI 2.84–23.03). These data emphasize that skin-barrier impairment due to reduced filaggrin expression plays an important role in the pathogenesis of AD and sheds further light on the genetic architecture of atopy in Japan.
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prevalent and rare mutations in the gene encoding filaggrin cause Ichthyosis vulgaris and predispose individuals to atopic dermatitis
Journal of Investigative Dermatology, 2006Co-Authors: Aileen Sandilands, Frances J D Smith, Ana Terronkwiatkowski, Yiwei Zhao, Haihui Liao, David Goudie, Rosemarie Watson, Grainne M Oregan, Andrew J Cassidy, W Irwin H McleanAbstract:Mutations in the filament aggregating protein (filaggrin) gene have recently been identified as the cause of the common genetic skin disorder Ichthyosis vulgaris (IV), the most prevalent inherited disorder of keratinization. The main characteristics of IV are fine-scale on the arms and legs, palmar hyperlinearity, and keratosis pilaris. Here, we have studied six Irish families with IV for mutations in filaggrin. We have identified a new mutation, 3702delG, in addition to further instances of the reported mutations R501X and 2282del4, which are common in people of European origin. A case of a 2282del4 homozygote was also identified. Mutation 3702delG terminates protein translation in filaggrin repeat domain 3, whereas both recurrent mutations occur in repeat 1. These mutations are semidominant: heterozygotes have an intermediate phenotype most readily identified by palmar hyperlinearity and in some cases fine-scale and/or keratosis pilaris, whereas homozygotes or compound heterozygotes generally have more marked Ichthyosis. Interestingly, the phenotypes of individuals homozygous for R501X, 2282del4, or compound heterozygous for R501X and 3702delG, were comparable, suggesting that mutations located centrally in the filaggrin repeats are also pathogenic.
Toshio Hamada - One of the best experts on this subject based on the ideXlab platform.
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twenty nail dystrophy trachyonychia caused by lichen planus in a patient with alopecia universalis and Ichthyosis vulgaris
Journal of The American Academy of Dermatology, 1995Co-Authors: Shoji Taniguchi, Haruo Kutsuna, Yukiko Tani, Kazuhiro Kawahira, Toshio HamadaAbstract:A 7-year-old girl with alopecia universalis had dystrophy of all 20 nails. A nail biopsy specimen disclosed features of lichen planus. The patient also had Ichthyosis vulgaris and hypogammaglobulinemia. We are not aware of any previous reports of these associations, which we believe to be noncoincidental.
Shoji Taniguchi - One of the best experts on this subject based on the ideXlab platform.
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twenty nail dystrophy trachyonychia caused by lichen planus in a patient with alopecia universalis and Ichthyosis vulgaris
Journal of The American Academy of Dermatology, 1995Co-Authors: Shoji Taniguchi, Haruo Kutsuna, Yukiko Tani, Kazuhiro Kawahira, Toshio HamadaAbstract:A 7-year-old girl with alopecia universalis had dystrophy of all 20 nails. A nail biopsy specimen disclosed features of lichen planus. The patient also had Ichthyosis vulgaris and hypogammaglobulinemia. We are not aware of any previous reports of these associations, which we believe to be noncoincidental.
S Stemmler - One of the best experts on this subject based on the ideXlab platform.
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on the role of the epidermal differentiation complex in Ichthyosis vulgaris atopic dermatitis and psoriasis
British Journal of Dermatology, 2007Co-Authors: S Hoffjan, S StemmlerAbstract:Summary Undisturbed epidermal differentiation is crucial for an intact skin barrier function. The epidermal differentiation complex (EDC) is a cluster of genes on chromosome 1q21 encoding proteins that fulfil important functions in terminal differentiation in the human epidermis, including filaggrin, loricrin, S100 proteins and others. Recently, evidence emerged that variation within EDC genes plays an important role in the pathogenesis of three common skin disorders, Ichthyosis vulgaris, atopic dermatitis (AD) and psoriasis. Two loss-of-function mutations in the filaggrin (FLG) gene, R501X and 2282del4, were identified as causative for Ichthyosis vulgaris in 15 affected European families, and the mode of inheritance was found to be semidominant. As Ichthyosis vulgaris and AD often occur concomitantly in affected individuals, these two mutations were subsequently investigated in AD patients and found to be strongly associated with the disease. Following this first report, seven replication studies have been performed that all confirm an association of these two mutations with AD (or AD subtypes) in several European cohorts. Additionally, two unique loss-of-function mutations in the FLG gene were identified in Japanese Ichthyosis vulgaris families and found to be associated with AD in a Japanese cohort. Thus, the FLG mutations are among the most consistently replicated associations for AD. Additionally, linkage analysis has suggested that variation within the EDC might also predispose for psoriasis but the exact susceptibility variation(s) have not yet been elucidated. Taken together, these findings convincingly demonstrate the important role of barrier dysfunction in various common skin disorders.
