Unique and recurrent mutations in the filaggrin gene in Singaporean Chinese patients with ichthyosis vulgaris

Huijia Chen, Jean C. C. Ho, Aileen Sandilands, Yuin Chew Chan, Yoke Chin Giam, Alan T. Evans, E. Birgitte Lane, W. H. Irwin McLean

    Research output: Contribution to journalArticle

    41 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)1669-1675
    Number of pages7
    JournalJournal of Investigative Dermatology
    Volume128
    Issue number7
    DOIs
    Publication statusPublished - Jul 2008

    Keywords

    • OF-FUNCTION MUTATIONS
    • X-LINKED ICHTHYOSIS
    • ATOPIC-DERMATITIS
    • IDENTIFICATION
    • PREDISPOSE
    • PHENOTYPES
    • BARRIER

    Cite this

    Chen, Huijia ; Ho, Jean C. C. ; Sandilands, Aileen ; Chan, Yuin Chew ; Giam, Yoke Chin ; Evans, Alan T. ; Lane, E. Birgitte ; McLean, W. H. Irwin. / Unique and recurrent mutations in the filaggrin gene in Singaporean Chinese patients with ichthyosis vulgaris. In: Journal of Investigative Dermatology. 2008 ; Vol. 128, No. 7. pp. 1669-1675.
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    Unique and recurrent mutations in the filaggrin gene in Singaporean Chinese patients with ichthyosis vulgaris. / Chen, Huijia; Ho, Jean C. C.; Sandilands, Aileen; Chan, Yuin Chew; Giam, Yoke Chin; Evans, Alan T.; Lane, E. Birgitte; McLean, W. H. Irwin.

    In: Journal of Investigative Dermatology, Vol. 128, No. 7, 07.2008, p. 1669-1675.

    Research output: Contribution to journalArticle

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    AU - Chen, Huijia

    AU - Ho, Jean C. C.

    AU - Sandilands, Aileen

    AU - Chan, Yuin Chew

    AU - Giam, Yoke Chin

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    AU - McLean, W. H. Irwin

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    AB - 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.

    KW - OF-FUNCTION MUTATIONS

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    KW - ATOPIC-DERMATITIS

    KW - IDENTIFICATION

    KW - PREDISPOSE

    KW - PHENOTYPES

    KW - BARRIER

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