Gene Expression Profiling in Pachyonychia Congenita Skin

Overview

Journal J Dermatol Sci

Publisher Elsevier

Specialty Dermatology

Date 2015 Feb 7

PMID 25656049

Citations 12

Authors

Yu-An Cao

Robyn P Hickerson

Brandon L Seegmiller

Dmitry Grapov

Maren M Gross

Marc R Bessette

Brett S Phinney

Manuel A Flores

Tycho J Speaker

Annaleen Vermeulen

Albert A Bravo

Anna L Bruckner

Leonard M Milstone

Mary E Schwartz

Robert H Rice

Roger L Kaspar

Affiliations

Soon will be listed here.

Abstract

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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