Generalized Epidermolytic Hyperkeratosis in Two Unrelated Children from Parents with Localized Linear Form, and Prenatal Diagnosis

Chassaing, Nicolas; Kanitakis, Jean; Sportich, S.; Cordier-Alex, Marie-Pierre; Titeux, Matthias; Calvas, P; Claudy, A; Berbis, P.; Hovnanian, Alain

doi:10.1038/sj.jid.5700553

Cited by 28 publications

(22 citation statements)

References 6 publications

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“…Mutations in Kl were found in 5 families, and 6 families had mutations in KIO. Six of these mutations have been described previously (3)(4)(5)(6)(7)(8). The remaining mutations are novel: 3 point mutations with a non-conservative amino acid substitution (family numbers 1,2 and 11) and 1 in-frame deletion of 30 bp in KRTl exon 2 (family number 5).…”

Section: Resultsmentioning

confidence: 96%

Generalized and Naevoid Epidermolytic Ichthyosis in Denmark: Clinical and Mutational Findings

Bygum¹,

Virtanen²,

Brandrup³

et al. 2013

Acta Derm Venerol

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A Danish-Swedish collaboration was established to identify and classify a Danish cohort of patients with epidermolytic ichthyosis, also known as epidermolytic hyperkeratosis. Patients were recruited from 5 dermatology departments in Denmark, and data were obtained using a structured questionnaire and a systematic examination together with photographs, histopathological descriptions and blood samples for mutational analysis. Sixteen patients from 12 families with generalized or naevoid epidermolytic ichthyosis and ichthyosis bullosa of Siemens were identified. Five families had mutations in K1 and 6 families had mutations in K10. Nine patients had been treated with systemic retinoids (etretinate, acitretin, isotretinoin or alitretinoin), but only 3 patients had acceptable treatment responses and chose to continue therapy. In conclusion epidermolytic ichthyosis is a rare disease with a prevalence of approximately 1 in 350,000 in Denmark and a high percentage of de novo mutations (75%). We identified 4 novel disease-causing mutations.

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Section: Resultsmentioning

confidence: 96%

Generalized and Naevoid Epidermolytic Ichthyosis in Denmark: Clinical and Mutational Findings

Bygum¹,

Virtanen²,

Brandrup³

et al. 2013

Acta Derm Venerol

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“…After the discovery of KRT10 mutations (Moss et al 1995;Paller et al 1994), a KRT1 mutation has recently also been identiWed (Tsubota et al 2007). Patients with the nevoid variant of BCIE who have children with full-blown BCIE have underlying gonadal as well as cutaneous mosaicism (Chassaing et al 2006;Reddy et al 1997). Besides mosaic BCIE, mosaicism has been described for EBS (Nagao-Watanabe et al 2004) and in a palmoplantar verrucous nevus (Terrinoni et al 2000).…”

Section: Keratoderma Disorders Caused By Keratin Mutationsmentioning

confidence: 97%

The molecular basis of human keratin disorders

Arin

2009

Hum Genet

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Keratins are cytoskeletal proteins that provide structural support to epithelial cells and tissues. Perturbation causes cell and tissue fragility and accounts for a large number of genetic disorders in humans. In humans, 54 functional keratin genes exist and 21 different keratin genes including hair keratins and hair follicle-specific epithelial keratins have been associated with hereditary disorders. Moreover, keratins have been implicated in more complex traits such as liver disease and inflammatory bowel disease. Understanding the molecular basis of keratin disorders has been the basis for improved diagnosis with prognostic implications, genetic counseling and prenatal testing for severe disorders. Besides their mechanical role, keratins have newly identified functions in apoptosis, cell growth, tissue polarity, wound healing and tissue remodeling. Improved understanding of the regulatory functions of keratins may offer novel approaches to overcome current treatment limitations.

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“…Mutant keratins negatively impact skin structure and function, at least in part, by destabilizing the existing intermediate filament networks within cells [13–15], resulting in faulty intermediate filaments and cell fragility, which can lead to skin disorders including epidermolytic ichthyosis (also known as epidermolytic hyperkeratosis, caused by keratin ( KRT ) 1/KRT10 gene mutations) [16, 17], epidermolysis bullosa simplex ( KRT5/KRT14 ) [18, 19], and PC ( KRT6A/6B/16/17 ) [1, 2, 5]. The majority of PC mutations are heterozygous missense or small insertion/deletion mutations that disrupt cytoskeletal function, presumably by preventing proper protein/protein interactions [20, 21].…”

Section: Introductionmentioning

confidence: 99%

Gene expression profiling in pachyonychia congenita skin

Cao¹,

Hickerson²,

Seegmiller³

et al. 2015

Journal of Dermatological Science

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Background Pachyonychia congenita (PC) is a skin disorder resulting from mutations in keratin (K) proteins including K6a, K6b, K16, and K17. One of the major symptoms is painful plantar keratoderma. The pathogenic sequelae resulting from the keratin mutations remain unclear. Objective To better understand PC pathogenesis. Methods RNA profiling was performed on biopsies taken from PC-involved and uninvolved plantar skin of seven genotyped PC patients (two K6a, one K6b, three K16, and one K17) as well as from control volunteers. Protein profiling was generated from tape-stripping samples. Results A comparison of PC-involved skin biopsies to adjacent uninvolved plantar skin identified 112 differentially-expressed mRNAs common to patient groups harboring K6 (i.e., both K6a and K6b) and K16 mutations. Among these mRNAs, 25 encode structural proteins including keratins, small proline-rich and late cornified envelope proteins, 20 are related to metabolism and 16 encode proteases, peptidases, and their inhibitors including kallikrein-related peptidases (KLKs), and serine protease inhibitors (SERPINs). mRNAs were also identified to be differentially expressed only in K6 (81) or K16 (141) patient samples. Furthermore, 13 mRNAs were identified that may be involved in pain including nociception and neuropathy. Protein profiling, comparing three K6a plantar tape-stripping samples to non-PC controls, showed changes in the PC corneocytes similar, but not identical, to the mRNA analysis. Conclusion Many differentially-expressed genes identified in PC-involved skin encode components critical for skin barrier homeostasis including keratinocyte proliferation, differentiation, cornification, and desquamation. The profiling data provide a foundation for unraveling the pathogenesis of PC and identifying targets for developing effective PC therapeutics.

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Generalized Epidermolytic Hyperkeratosis in Two Unrelated Children from Parents with Localized Linear Form, and Prenatal Diagnosis

Cited by 28 publications

References 6 publications

Generalized and Naevoid Epidermolytic Ichthyosis in Denmark: Clinical and Mutational Findings

Generalized and Naevoid Epidermolytic Ichthyosis in Denmark: Clinical and Mutational Findings

The molecular basis of human keratin disorders

Gene expression profiling in pachyonychia congenita skin

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