The molecular skin pathology of familial primary localized cutaneous amyloidosis

Akio Tanaka, Joey E. Lai-Cheong, Peter C. van den Akker, Nikoletta Nagy, George Millington, Gilles F. H. Diercks, Pieter C. van Voorst Vader, Suzanne E. Clements, Noor Almaani, Tanasit Techanukul, Michihiro Hide, Andrew P. South, John A. McGrath

    Research output: Contribution to journalArticlepeer-review

    34 Citations (Scopus)


    Familial primary localized cutaneous amyloidosis (FPLCA) is an autosomal dominant disorder associated with chronic itching and skin lichenification. In lesional skin, there are apoptotic basal keratinocytes and deposits of amyloid material on degenerate keratin filaments in the upper dermis. The genetic basis of FPLCA involves mutations in the OSMR and IL31RA genes but the disease pathophysiology is not fully understood. In this study, we identified new pathogenic heterozygous missense mutations in the OSMR gene (p.Val631Leu and p.Asp647Tyr) in two Dutch FPLCA families. We then compared gene expression profiles between FPLCA lesional skin (n = 4) and site-matched control skin (n = 6). There was twofold or greater upregulation of 34 genes and downregulation of 43 genes. Most changes in gene expression (verified by quantitative RT-PCR) reflected alterations in epidermal differentiation and proliferation consistent with lichenification, but we also noted a reduction in several interfollicular keratinocyte stem cell markers in FPLCA skin. Differences in gene expression were also noted for proteins involved in apoptosis and nerve conduction. Collectively, this study expands the molecular basis of FPLCA and provides new insight into the skin pathology of this condition.

    Original languageEnglish
    Pages (from-to)416-423
    Number of pages8
    JournalExperimental Dermatology
    Issue number5
    Publication statusPublished - May 2010


    • apoptosis
    • gene expression
    • interleukin 31
    • oncostatin M
    • pruritus
    • CELLS
    • GENE


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