Epidermolysis bullosa simplex in Scotland caused by a spectrum of keratin mutations

Elizabeth L Rugg, Helen M Horn, Frances J. Smith, Neil J. Wilson, Alison J. M. Hill, Gareth J. Magee, Carrie S. Shemanko, David U. Baty, Michael J. Tidman, E. Birgitte Lane

    Research output: Contribution to journalArticle

    39 Citations (Scopus)

    Abstract

    Epidermolysis bullosa simplex (EBS) is an inherited skin disorder caused by mutations in keratins K5 (keratin 5) and K14 (keratin 14), with fragility of basal keratinocytes leading to epidermal cytolysis and blistering. Patients present with widely varying severity and are classified in three main subtypes: EBS Weber-Cockayne (EBS-WC), EBS Köbner (EBS-K), and EBS Dowling-Meara (EBS-DM), based on distribution and pattern of blisters. We could identify K5/K14 mutations in 20 out of the 43 families registered as affected by dominant EBS in Scotland; with previous studies this covers 70% of all Scottish EBS patients, making this the most comprehensively analyzed EBS population. Nine mutations are novel. All mutations lie within five previously identified rod domain hotspots and the severest blistering was associated with mutations in the helix boundary motifs. In some cases, the same mutation caused symptoms of EBS-WC and/or EBS-K, both within and between families, suggesting a contribution of additional factors to the phenotype. In some patients, no mutations were found in K5, K14, or K15, suggesting involvement of other genes. The results confirm that EBS is best considered as a single disorder with a spectrum of phenotypic variations, from severe EBS-DM at one extreme to mild EBS-WC at the other.
    Original languageEnglish
    Pages (from-to)574-80
    Number of pages7
    JournalJournal of Investigative Dermatology
    Volume127
    Issue number3
    DOIs
    Publication statusPublished - 2007

    Fingerprint

    Epidermolysis Bullosa Simplex
    Keratin-14
    Keratin-5
    Scotland
    Keratins
    Mutation
    Skin
    Genes
    Blister
    Keratinocytes

    Keywords

    • Adolescent
    • Adult
    • Aged
    • Child
    • Child, Preschool
    • Epidermolysis Bullosa Simplex
    • Genetics, Population
    • Humans
    • Infant
    • Keratin-14
    • Keratin-5
    • Middle Aged
    • Mutation
    • Phenotype
    • Scotland

    Cite this

    Rugg, Elizabeth L ; Horn, Helen M ; Smith, Frances J. ; Wilson, Neil J. ; Hill, Alison J. M. ; Magee, Gareth J. ; Shemanko, Carrie S. ; Baty, David U. ; Tidman, Michael J. ; Lane, E. Birgitte. / Epidermolysis bullosa simplex in Scotland caused by a spectrum of keratin mutations. In: Journal of Investigative Dermatology. 2007 ; Vol. 127, No. 3. pp. 574-80.
    @article{517296d650c642428c7c788c7495e59a,
    title = "Epidermolysis bullosa simplex in Scotland caused by a spectrum of keratin mutations",
    abstract = "Epidermolysis bullosa simplex (EBS) is an inherited skin disorder caused by mutations in keratins K5 (keratin 5) and K14 (keratin 14), with fragility of basal keratinocytes leading to epidermal cytolysis and blistering. Patients present with widely varying severity and are classified in three main subtypes: EBS Weber-Cockayne (EBS-WC), EBS K{\"o}bner (EBS-K), and EBS Dowling-Meara (EBS-DM), based on distribution and pattern of blisters. We could identify K5/K14 mutations in 20 out of the 43 families registered as affected by dominant EBS in Scotland; with previous studies this covers 70{\%} of all Scottish EBS patients, making this the most comprehensively analyzed EBS population. Nine mutations are novel. All mutations lie within five previously identified rod domain hotspots and the severest blistering was associated with mutations in the helix boundary motifs. In some cases, the same mutation caused symptoms of EBS-WC and/or EBS-K, both within and between families, suggesting a contribution of additional factors to the phenotype. In some patients, no mutations were found in K5, K14, or K15, suggesting involvement of other genes. The results confirm that EBS is best considered as a single disorder with a spectrum of phenotypic variations, from severe EBS-DM at one extreme to mild EBS-WC at the other.",
    keywords = "Adolescent, Adult, Aged, Child, Child, Preschool, Epidermolysis Bullosa Simplex, Genetics, Population, Humans, Infant, Keratin-14, Keratin-5, Middle Aged, Mutation, Phenotype, Scotland",
    author = "Rugg, {Elizabeth L} and Horn, {Helen M} and Smith, {Frances J.} and Wilson, {Neil J.} and Hill, {Alison J. M.} and Magee, {Gareth J.} and Shemanko, {Carrie S.} and Baty, {David U.} and Tidman, {Michael J.} and Lane, {E. Birgitte}",
    year = "2007",
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    language = "English",
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    Rugg, EL, Horn, HM, Smith, FJ, Wilson, NJ, Hill, AJM, Magee, GJ, Shemanko, CS, Baty, DU, Tidman, MJ & Lane, EB 2007, 'Epidermolysis bullosa simplex in Scotland caused by a spectrum of keratin mutations', Journal of Investigative Dermatology, vol. 127, no. 3, pp. 574-80. https://doi.org/10.1038/sj.jid.5700571

    Epidermolysis bullosa simplex in Scotland caused by a spectrum of keratin mutations. / Rugg, Elizabeth L; Horn, Helen M; Smith, Frances J.; Wilson, Neil J.; Hill, Alison J. M.; Magee, Gareth J.; Shemanko, Carrie S.; Baty, David U.; Tidman, Michael J.; Lane, E. Birgitte.

    In: Journal of Investigative Dermatology, Vol. 127, No. 3, 2007, p. 574-80.

    Research output: Contribution to journalArticle

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    AU - Rugg, Elizabeth L

    AU - Horn, Helen M

    AU - Smith, Frances J.

    AU - Wilson, Neil J.

    AU - Hill, Alison J. M.

    AU - Magee, Gareth J.

    AU - Shemanko, Carrie S.

    AU - Baty, David U.

    AU - Tidman, Michael J.

    AU - Lane, E. Birgitte

    PY - 2007

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    N2 - Epidermolysis bullosa simplex (EBS) is an inherited skin disorder caused by mutations in keratins K5 (keratin 5) and K14 (keratin 14), with fragility of basal keratinocytes leading to epidermal cytolysis and blistering. Patients present with widely varying severity and are classified in three main subtypes: EBS Weber-Cockayne (EBS-WC), EBS Köbner (EBS-K), and EBS Dowling-Meara (EBS-DM), based on distribution and pattern of blisters. We could identify K5/K14 mutations in 20 out of the 43 families registered as affected by dominant EBS in Scotland; with previous studies this covers 70% of all Scottish EBS patients, making this the most comprehensively analyzed EBS population. Nine mutations are novel. All mutations lie within five previously identified rod domain hotspots and the severest blistering was associated with mutations in the helix boundary motifs. In some cases, the same mutation caused symptoms of EBS-WC and/or EBS-K, both within and between families, suggesting a contribution of additional factors to the phenotype. In some patients, no mutations were found in K5, K14, or K15, suggesting involvement of other genes. The results confirm that EBS is best considered as a single disorder with a spectrum of phenotypic variations, from severe EBS-DM at one extreme to mild EBS-WC at the other.

    AB - Epidermolysis bullosa simplex (EBS) is an inherited skin disorder caused by mutations in keratins K5 (keratin 5) and K14 (keratin 14), with fragility of basal keratinocytes leading to epidermal cytolysis and blistering. Patients present with widely varying severity and are classified in three main subtypes: EBS Weber-Cockayne (EBS-WC), EBS Köbner (EBS-K), and EBS Dowling-Meara (EBS-DM), based on distribution and pattern of blisters. We could identify K5/K14 mutations in 20 out of the 43 families registered as affected by dominant EBS in Scotland; with previous studies this covers 70% of all Scottish EBS patients, making this the most comprehensively analyzed EBS population. Nine mutations are novel. All mutations lie within five previously identified rod domain hotspots and the severest blistering was associated with mutations in the helix boundary motifs. In some cases, the same mutation caused symptoms of EBS-WC and/or EBS-K, both within and between families, suggesting a contribution of additional factors to the phenotype. In some patients, no mutations were found in K5, K14, or K15, suggesting involvement of other genes. The results confirm that EBS is best considered as a single disorder with a spectrum of phenotypic variations, from severe EBS-DM at one extreme to mild EBS-WC at the other.

    KW - Adolescent

    KW - Adult

    KW - Aged

    KW - Child

    KW - Child, Preschool

    KW - Epidermolysis Bullosa Simplex

    KW - Genetics, Population

    KW - Humans

    KW - Infant

    KW - Keratin-14

    KW - Keratin-5

    KW - Middle Aged

    KW - Mutation

    KW - Phenotype

    KW - Scotland

    U2 - 10.1038/sj.jid.5700571

    DO - 10.1038/sj.jid.5700571

    M3 - Article

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    SP - 574

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    ER -