title: Gene expression profiling in pachyonychia congenita skin.
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.
  
  
  CONCLUSIONS
  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.
authors: TransDerm Inc., Santa Cruz, CA 95060, USA.
authors: Yu-An
authors: YA
authors: Cao
authors: TransDerm Inc., Santa Cruz, CA 95060, USA.
authors: Robyn P
authors: RP
authors: Hickerson
authors: TransDerm Inc., Santa Cruz, CA 95060, USA.
authors: Brandon L
authors: BL
authors: Seegmiller
authors: University of California at Davis, Davis, CA 95616, USA.
authors: Dmitry
authors: D
authors: Grapov
authors: Dharmacon part of GE Healthcare, Lafayette, CO 80026, USA.
authors: Maren M
authors: MM
authors: Gross
authors: Dharmacon part of GE Healthcare, Lafayette, CO 80026, USA.
authors: Marc R
authors: MR
authors: Bessette
authors: University of California at Davis, Davis, CA 95616, USA.
authors: Brett S
authors: BS
authors: Phinney
authors: TransDerm Inc., Santa Cruz, CA 95060, USA.
authors: Manuel A
authors: MA
authors: Flores
authors: TransDerm Inc., Santa Cruz, CA 95060, USA.
authors: Tycho J
authors: TJ
authors: Speaker
authors: Dharmacon part of GE Healthcare, Lafayette, CO 80026, USA.
authors: Annaleen
authors: A
authors: Vermeulen
authors: Podiatric Medicine and Surgery, Pittsfield, MA 01201, USA.
authors: Albert A
authors: AA
authors: Bravo
authors: University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors: Anna L
authors: AL
authors: Bruckner
authors: Yale University, New Haven, CT 06520, USA.
authors: Leonard M
authors: LM
authors: Milstone
authors: Pachyonychia Congenita Project, Salt Lake City, UT 84109, USA.
authors: Mary E
authors: ME
authors: Schwartz
authors: University of California at Davis, Davis, CA 95616, USA.
authors: Robert H
authors: RH
authors: Rice
authors: TransDerm Inc., Santa Cruz, CA 95060, USA. Electronic address: roger.kaspar@transderminc.com.
authors: Roger L
authors: RL
authors: Kaspar
mesh_terms: D015536:Down-Regulation; D004798:Enzymes / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D053536:Keratin-16 / Q000235:genetics; D053537:Keratin-17 / Q000235:genetics; D053553:Keratin-6 / Q000235:genetics; D007633:Keratins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D053549:Pachyonychia Congenita / Q000150:complications / Q000235:genetics*; D010146:Pain / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis*; D059467:Transcriptome; D015854:Up-Regulation
chemical_list: D004798:Enzymes; D053536:Keratin-16; D053537:Keratin-17; D053553:Keratin-6; D012333:RNA, Messenger; D007633:Keratins
keywords: Desquamation; Genodermatosis; Keratinocyte; Monogenic skin disorder; Painful palmoplantar keratoderma; mTOR signaling pathway
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