The molecular skin pathology of familial primary localized cutaneous amyloidosis

Akio Tanaka, Joey E. Lai-Cheong, Peter C. van den Akker, N. 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 journalArticle

27 Citations (Scopus)

Abstract

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
Volume19
Issue number5
DOIs
Publication statusPublished - May 2010

Fingerprint

Molecular Pathology
Pathology
Skin
Genes
Gene expression
Keratinocytes
Gene Expression
Neural Conduction
Amyloid Plaques
Missense Mutation
Pruritus
Dermis
Keratins
Stem cells
Transcriptome
Amyloid
Primary Cutaneous Amyloidosis
Up-Regulation
Stem Cells
Down-Regulation

Keywords

  • Apoptosis
  • Gene expression
  • Interleukin 31
  • Oncostatin M
  • Pruritus

ASJC Scopus subject areas

  • Dermatology
  • Molecular Biology
  • Biochemistry

Cite this

Tanaka, A., Lai-Cheong, J. E., van den Akker, P. C., Nagy, N., Millington, G., Diercks, G. F. H., ... McGrath, J. A. (2010). The molecular skin pathology of familial primary localized cutaneous amyloidosis. Experimental Dermatology, 19(5), 416-423. https://doi.org/10.1111/j.1600-0625.2010.01083.x

The molecular skin pathology of familial primary localized cutaneous amyloidosis. / Tanaka, Akio; Lai-Cheong, Joey E.; van den Akker, Peter C.; Nagy, N.; Millington, George; Diercks, Gilles F H; van Voorst Vader, Pieter C.; Clements, Suzanne E.; Almaani, Noor; Techanukul, Tanasit; Hide, Michihiro; South, Andrew P.; McGrath, John A.

In: Experimental Dermatology, Vol. 19, No. 5, 05.2010, p. 416-423.

Research output: Contribution to journalArticle

Tanaka, A, Lai-Cheong, JE, van den Akker, PC, Nagy, N, Millington, G, Diercks, GFH, van Voorst Vader, PC, Clements, SE, Almaani, N, Techanukul, T, Hide, M, South, AP & McGrath, JA 2010, 'The molecular skin pathology of familial primary localized cutaneous amyloidosis', Experimental Dermatology, vol. 19, no. 5, pp. 416-423. https://doi.org/10.1111/j.1600-0625.2010.01083.x
Tanaka, Akio ; Lai-Cheong, Joey E. ; van den Akker, Peter C. ; Nagy, N. ; Millington, George ; Diercks, Gilles F H ; van Voorst Vader, Pieter C. ; Clements, Suzanne E. ; Almaani, Noor ; Techanukul, Tanasit ; Hide, Michihiro ; South, Andrew P. ; McGrath, John A. / The molecular skin pathology of familial primary localized cutaneous amyloidosis. In: Experimental Dermatology. 2010 ; Vol. 19, No. 5. pp. 416-423.
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