951
Views
11
CrossRef citations to date
0
Altmetric
REVIEW ARTICLE

Inherited blistering skin diseases: underlying molecular mechanisms and emerging therapies

, &
Pages 49-61 | Received 30 Sep 2013, Accepted 07 Nov 2013, Published online: 22 Jan 2014

References

  • Simpson CL, Patel DM, Green KJ. Deconstructing the skin: cytoarchitectural determinants of epidermal morphogenesis. Nat Rev Mol Cell Biol. 2011;12:565–80.
  • Elias PM. Skin barrier function. Curr Allergy Asthma Rep. 2008;8: 299–305.
  • Tsuruta D, Hashimoto T, Hamill KJ, Jones JC. Hemidesmosomes and focal contact proteins: functions and cross-talk in keratinocytes, bullous diseases and wound healing. J Dermatol Sci. 2011; 62:1–7.
  • Green KJ, Getsios S, Troyanovsky S, Godsel LM. Intercellular junction assembly, dynamics, and homeostasis. Cold Spring Harb Perspect Biol. 2010;2:a000125.
  • Fine JD, Eady RA, Bauer EA, Bauer JW, Bruckner-Tuderman L, Heagerty A, et al. The classification of inherited epidermolysis bullosa (EB): report of the Third International Consensus Meeting on Diagnosis and Classification of EB. J Am Acad Dermatol. 2008;58: 931–50.
  • Bruckner-Tuderman L, McGrath JA, Robinson EC, Uitto J. Progress in epidermolysis bullosa research: Summary of DEBRA International Research Conference 2012. J Invest Dermatol. 2013;133:2121–6.
  • Pearson RW. Studies on the pathogenesis of epidermolysis bullosa. J Invest Dermatol. 1962;39:551–75.
  • Kim S, Coulombe PA. Intermediate filament scaffolds fulfill mechanical, organizational, and signaling functions in the cytoplasm. Genes Dev. 2007;21:1581–97.
  • Celli A, Sanchez S, Behne M, Hazlett T, Gratton E, Mauro T. The epidermal Ca(2+) gradient: measurement using the phasor representation of fluorescent lifetime imaging. Biophys J. 2010;98:911–21.
  • Coulombe PA, Lee CH. Defining keratin protein function in skin epithelia: epidermolysis bullosa simplex and its aftermath. J Invest Dermatol. 2012;132:763–75.
  • McLean WH, Moore CB. Keratin disorders: from gene to therapy. Hum Mol Genet. 2011;20:R189–97.
  • Sprecher E. Epidermolysis bullosa simplex. Dermatol Clin. 2010;28: 23–32.
  • Rezniczek GA, Walko G, Wiche G. Plectin gene defects lead to various forms of epidermolysis bullosa simplex. Dermatol Clin. 2010;28: 33–41.
  • Winter L, Wiche G. The many faces of plectin and plectinopathies: pathology and mechanisms. Acta Neuropathol. 2013;125:77–93.
  • McLean WH, Pulkkinen L, Smith FJ, Rugg EL, Lane EB, Bullrich F, et al. Loss of plectin causes epidermolysis bullosa with muscular dystrophy: cDNA cloning and genomic organization. Genes Dev. 1996; 10:1724–35.
  • Smith FJ, Eady RA, Leigh IM, McMillan JR, Rugg EL, Kelsell DP, et al. Plectin deficiency results in muscular dystrophy with epidermolysis bullosa. Nat Genet. 1996;13:450–7.
  • Charlesworth A, Chiaverini C, Chevrant-Breton J, DelRio M, Diociaiuti A, Dupuis RP, et al. Epidermolysis bullosa simplex with PLEC mutations: new phenotypes and new mutations. Br J Dermatol. 2013;168:808–14.
  • Bolling MC, Jongbloed JD, Boven LG, Diercks GF, Smith FJ, McLean WH, et al. Plectin mutations underlie epidermolysis bullosa simplex in 8% of patients. J Invest Dermatol. 2014;134:273–6.
  • Kligys KR, Wu Y, Hopkinson SB, Kaur S, Platanias LC, Jones JC.α6β4 Integrin, a master regulator of expression of integrins in human keratinocytes. J Biol Chem. 2012;287:17975–84.
  • Margadant C, Charafeddine RA, Sonnenberg A. Unique and redundant functions of integrins in the epidermis. FASEB J. 2010;24:4133–52.
  • Chung HJ, Uitto J. Type VII collagen: the anchoring fibril protein at fault in dystrophic epidermolysis bullosa. Dermatol Clin. 2010;28: 93–105.
  • Ashton GH, Sorelli P, Mellerio JE, Keane FM, Eady RA, McGrath JA. Alpha 6 beta 4 integrin abnormalities in junctional epidermolysis bullosa with pyloric atresia. Br J Dermatol. 2001;144:408–14.
  • Inoue M, Tamai K, Shimizu H, Owaribe K, Nakama T, Hashimoto T, et al. A homozygous missense mutation in the cytoplasmic tail of beta4 integrin, G931D, that disrupts hemidesmosome assembly and underlies non-Herlitz junctional epidermolysis bullosa without pyloric atresia?J Invest Dermatol. 2000;114:1061–4.
  • Sugawara K, Tsuruta D, Ishii M, Jones JC, Kobayashi H. Laminin-332 and -511 in skin. Exp Dermatol. 2008;17:473–80.
  • Kiritsi D, Has C, Bruckner-Tuderman L. Laminin 332 in junctional epidermolysis bullosa. Cell Adh Migr. 2013;7:135–41.
  • Laimer M, Lanschuetzer CM, Diem A, Bauer JW. Herlitz junctional epidermolysis bullosa. Dermatol Clin. 2010;28:55–60.
  • Yancey KB, Hintner H. Non-Herlitz junctional epidermolysis bullosa. Dermatol Clin. 2010;28:67–77.
  • McLean WH, Irvine AD, Hamill KJ, Whittock NV, Coleman-Campbell CM, Mellerio JE, et al. An unusual N-terminal deletion of the laminin alpha3a isoform leads to the chronic granulation tissue disorder laryngo-onycho-cutaneous syndrome. Hum Mol Genet. 2003;12: 2395–409.
  • Powell AM, Sakuma-Oyama Y, Oyama N, Black MM. Collagen XVII/BP180: a collagenous transmembrane protein and component of the dermoepidermal anchoring complex. Clin Exp Dermatol. 2005;30: 682–7.
  • Schmidt E, Zillikens D. Pemphigoid diseases. Lancet. 2013;381: 320–32.
  • McGrath JA, Gatalica B, Christiano AM, Li K, Owaribe K, McMillan JR, et al. Mutations in the 180-kD bullous pemphigoid antigen (BPAG2), a hemidesmosomal transmembrane collagen (COL17A1), in generalized atrophic benign epidermolysis bullosa. Nat Genet. 1995;11:83–6.
  • McGrath JA, Gatalica B, Li K, Dunnill MG, McMillan JR, Christiano AM, et al. Compound heterozygosity for a dominant glycine substitution and a recessive internal duplication mutation in the type XVII collagen gene results in junctional epidermolysis bullosa and abnormal dentition. Am J Pathol. 1996;148:1787–96.
  • Almaani N, Liu L, Dopping-Hepenstal PJ, Lovell PA, Lai-Cheong JE, Graham RM, et al. Autosomal dominant junctional epidermolysis bullosa. Br J Dermatol. 2009;160:1094–7.
  • Burgeson RE, Lunstrum GP, Rokosova B, Rimberg CS, Rosenbaum LM, Keene DR. The structure and function of type VII collagen. Ann N Y Acad Sci. 1990;580:32–43.
  • Tidman MJ, Eady RA. Ultrastructural morphometry of normal human dermal-epidermal junction. The influence of age, sex, and body region on laminar and nonlaminar components. J Invest Dermatol. 1984;83: 448–53.
  • Christiano AM, Suga Y, Greenspan DS, Ogawa H, Uitto J. Premature termination codons on both alleles of the type VII collagen gene (COL7A1) in three brothers with recessive dystrophic epidermolysis bullosa. J Clin Invest. 1995;95:1328–34.
  • Fine JD, Mellerio JE. Extracutaneous manifestations and complications of inherited epidermolysis bullosa: part I. Epithelial associated tissues. J Am Acad Dermatol. 2009;61:367–84.
  • Christiano AM, McGrath JA, Tan KC, Uitto J. Glycine substitutions in the triple-helical region of type VII collagen result in a spectrum of dystrophic epidermolysis bullosa phenotypes and patterns of inheritance. Am J Hum Genet. 1996;58:671–81.
  • Christiano AM, Ryynanen M, Uitto J. Dominant dystrophic epidermolysis bullosa: identification of a Gly--> Ser substitution in the triple-helical domain of type VII collagen. Proc Natl Acad Sci U S A. 1994;91:3549–53.
  • Meves A, Stremmel C, Gottschalk K, Fassler R. The Kindlin protein family: new members to the club of focal adhesion proteins. Trends Cell Biol. 2009;19:504–13.
  • Lai-Cheong JE, Parsons M, McGrath JA. The role of kindlins in cell biology and relevance to human disease. Int J Biochem Cell Biol. 2010;42:595–603.
  • Jobard F, Bouadjar B, Caux F, Hadj-Rabia S, Has C, Matsuda F, et al. Identification of mutations in a new gene encoding a FERM family protein with a pleckstrin homology domain in Kindler syndrome. Hum Mol Genet. 2003;12:925–35.
  • Siegel DH, Ashton GH, Penagos HG, Lee JV, Feiler HS, Wilhelmsen KC, et al. Loss of kindlin-1, a human homolog of the Caenorhabditis elegans actin-extracellular-matrix linker protein UNC-112, causes Kindler syndrome. Am J Hum Genet. 2003;73: 174–87.
  • Lai-Cheong JE, Tanaka A, Hawche G, Emanuel P, Maari C, Taskesen M, et al. Kindler syndrome: a focal adhesion genodermatosis. Br J Dermatol. 2009;160:233–42.
  • Kowalczyk AP, Green KJ. Structure, function, and regulation of desmosomes. Prog Mol Biol Transl Sci. 2013;116:95–118.
  • Nekrasova O, Green KJ. Desmosome assembly and dynamics. Trends Cell Biol. 2013;23:537–46.
  • McGrath JA, McMillan JR, Shemanko CS, Runswick SK, Leigh IM, Lane EB, et al. Mutations in the plakophilin 1 gene result in ectodermal dysplasia/skin fragility syndrome. Nat Genet. 1997;17:240–4.
  • South AP, Wan H, Stone MG, Dopping-Hepenstal PJ, Purkis PE, Marshall JF, et al. Lack of plakophilin 1 increases keratinocyte migration and reduces desmosome stability. J Cell Sci. 2003;116:3303–14.
  • Hatzfeld M. Plakophilins: multifunctional proteins or just regulators of desmosomal adhesion?Biochim Biophys Acta. 2007;1773:69–77.
  • Wolf A, Hatzfeld M. A role of plakophilins in the regulation of translation. Cell Cycle. 2010;9:2973–8.
  • Garrod D, Chidgey M. Desmosome structure, composition and function. Biochim Biophys Acta. 2008;1778:572–87.
  • Armstrong DK, McKenna KE, Purkis PE, Green KJ, Eady RA, Leigh IM, et al. Haploinsufficiency of desmoplakin causes a striate subtype of palmoplantar keratoderma. Hum Mol Genet. 1999;8: 143–8.
  • Rizzo S, Pilichou K, Thiene G, Basso C. The changing spectrum of arrhythmogenic (right ventricular) cardiomyopathy. Cell Tissue Res. 2012;348:319–23.
  • Petrof G, Mellerio JE, McGrath JA. Desmosomal genodermatoses. Br J Dermatol. 2012;166:36–45.
  • Jonkman MF, Pasmooij AM, Pasmans SG, van den Berg MP, Ter Horst HJ, Timmer A, et al. Loss of desmoplakin tail causes lethal acantholytic epidermolysis bullosa. Am J Hum Genet. 2005;77:653–60.
  • Hobbs RP, Han SY, van der Zwaag PA, Bolling MC, Jongbloed JD, Jonkman MF, et al. Insights from a desmoplakin mutation identified in lethal acantholytic epidermolysis bullosa. J Invest Dermatol. 2010;130:2680–3.
  • Groves RW, Liu L, Dopping-Hepenstal PJ, Markus HS, Lovell PA, Ozoemena L, et al. A homozygous nonsense mutation within the dystonin gene coding for the coiled-coil domain of the epithelial isoform of BPAG1 underlies a new subtype of autosomal recessive epidermolysis bullosa simplex. J Invest Dermatol. 2010;130:1551–7.
  • Liu L, Dopping-Hepenstal PJ, Lovell PA, Michael M, Horn H, Fong K, et al. Autosomal recessive epidermolysis bullosa simplex due to loss of BPAG1-e expression. J Invest Dermatol. 2012;132:742–4.
  • Michael M, Begum R, Fong K, Pourreyrone C, South AP, McGrath JA, et al. BPAG1-e restricts keratinocyte migration through control of adhesion stability. J Invest Dermatol.2013 Sep 11 [Epub ahead of print].
  • Hodivala-Dilke KM, DiPersio CM, Kreidberg JA, Hynes RO. Novel roles for alpha3beta1 integrin as a regulator of cytoskeletal assembly and as a trans-dominant inhibitor of integrin receptor function in mouse keratinocytes. J Cell Biol. 1998;142:1357–69.
  • Has C, Sparta G, Kiritsi D, Weibel L, Moeller A, Vega-Warner V, et al. Integrin alpha3 mutations with kidney, lung, and skin disease. N Engl J Med. 2012;366:1508–14.
  • Yin T, Green KJ. Regulation of desmosome assembly and adhesion. Semin Cell Dev Biol. 2004;15:665–77.
  • McKoy G, Protonotarios N, Crosby A, Tsatsopoulou A, Anastasakis A, Coonar A, et al. Identification of a deletion in plakoglobin in arrhythmogenic right ventricular cardiomyopathy with palmoplantar keratoderma and woolly hair (Naxos disease). Lancet. 2000;355:2119–24.
  • Azaouagh A, Churzidse S, Konorza T, Erbel R. Arrhythmogenic right ventricular cardiomyopathy/dysplasia: a review and update. Clin Res Cardiol. 2011;100:383–94.
  • Li D, Liu Y, Maruyama M, Zhu W, Chen H, Zhang W, et al. Restrictive loss of plakoglobin in cardiomyocytes leads to arrhythmogenic cardiomyopathy. Hum Mol Genet. 2011;20:4582–96.
  • Winik BC, Asial RA, McGrath JA, South AP, Boente MC. Acantholytic ectodermal dysplasia: clinicopathological study of a new desmosomal disorder. Br J Dermatol. 2009;160:868–74.
  • Cabral RM, Liu L, Hogan C, Dopping-Hepenstal PJ, Winik BC, Asial RA, et al. Homozygous mutations in the 5’ region of the JUP gene result in cutaneous disease but normal heart development in children. J Invest Dermatol. 2010;130:1543–50.
  • Pigors M, Kiritsi D, Krumpelmann S, Wagner N, He Y, Podda M, et al. Lack of plakoglobin leads to lethal congenital epidermolysis bullosa: a novel clinico-genetic entity. Hum Mol Genet. 2011;20:1811–19.
  • McGrath JA, Stone KL, Begum R, Simpson MA, Dopping-Hepenstal PJ, Liu L, et al. Germline mutation in EXPH5 implicates the Rab27B effector protein Slac2-b in inherited skin fragility. Am J Hum Genet. 2012;91:1115–21.
  • Stenmark H. Rab GTPases as coordinators of vesicle traffic. Nat Rev Mol Cell Biol. 2009;10:513–25.
  • Pigors M, Schwieger-Briel A, Leppert J, Kiritsi D, Kohlhase J, Bruckner-Tuderman L, et al. Molecular heterogeneity of epidermolysis bullosa simplex: contribution of EXPH5 mutations. J Invest Dermatol.2013 Sep 4 [Epub ahead of print].
  • Liu L, Mellerio JE, Martinez AE, McMillan JR, Aristodemou S, Parsons M, et al. Mutations in EXPH5 result in autosomal recessive skin fragility. Br J Dermatol. 2014;170:204–7.
  • Cassidy AJ, van Steensel MA, Steijlen PM, van Geel M, van der Velden J, Morley SM, et al. A homozygous missense mutation in TGM5 abolishes epidermal transglutaminase 5 activity and causes acral peeling skin syndrome. Am J Hum Genet. 2005;77:909–17.
  • Pietroni V, Di Giorgi S, Paradisi A, Ahvazi B, Candi E, Melino G. Inactive and highly active, proteolytically processed transglutaminase-5 in epithelial cells. J Invest Dermatol. 2008;128:2760–6.
  • Kharfi M, El Fekih N, Ammar D, Jaafoura H, Schwonbeck S, van Steensel MA, et al. A missense mutation in TGM5 causes acral peeling skin syndrome in a Tunisian family. J Invest Dermatol. 2009;129:2512–15.
  • Kiritsi D, Cosgarea I, Franzke CW, Schumann H, Oji V, Kohlhase J, et al. Acral peeling skin syndrome with TGM5 gene mutations may resemble epidermolysis bullosa simplex in young individuals. J Invest Dermatol. 2010;130:1741–6.
  • van der Velden JJ, Jonkman MF, McLean WH, Hamm H, Steijlen PM, van Steensel MA, et al. A recurrent mutation in the TGM5 gene in European patients with acral peeling skin syndrome. J Dermatol Sci. 2012;65:74–6.
  • Chen J, Den Z, Koch PJ. Loss of desmocollin 3 in mice leads to epidermal blistering. J Cell Sci. 2008;121:2844–9.
  • Ayub M, Basit S, Jelani M, Ur Rehman F, Iqbal M, Yasinzai, et al. A homozygous nonsense mutation in the human desmocollin-3 (DSC3) gene underlies hereditary hypotrichosis and recurrent skin vesicles. Am J Hum genet. 2009;85:515–20.
  • Hammers CM, Stanley JR. Desmoglein-1, differentiation, and disease. J Clin Invest. 2013;123:1419–22.
  • Amagai M, Stanley JR. Desmoglein as a target in skin disease and beyond. J Invest Dermatol. 2012;132:776–84.
  • Rickman L, Simrak D, Stevens HP, Hunt DM, King IA, Bryant SP, et al. N-terminal deletion in a desmosomal cadherin causes the autosomal dominant skin disease striate palmoplantar keratoderma. Hum Mol Genet. 1999;8:971–6.
  • Zamiri M, Smith FJ, Campbell LE, Tetley L, Eady RA, Hodgins MB, et al. Mutation in DSG1 causing autosomal dominant striate palmoplantar keratoderma. Br J Dermatol. 2009;161:692–4.
  • Samuelov L, Sarig O, Harmon RM, Rapaport D, Ishida-Yamamoto A, Isakov O, et al. Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting. Nat Genet. 2013;45:1244–8.
  • Jonca N, Guerrin M, Hadjiolova K, Caubet C, Gallinaro H, Simon M, et al. Corneodesmosin, a component of epidermal corneocyte desmosomes, displays homophilic adhesive properties. J Biol Chem. 2002; 277:5024–9.
  • Simon M, Jonca N, Guerrin M, Haftek M, Bernard D, Caubet C, et al. Refined characterization of corneodesmosin proteolysis during terminal differentiation of human epidermis and its relationship to desquamation. J Biol Chem. 2001;276:20292–9.
  • Levy-Nissenbaum E, Betz RC, Frydman M, Simon M, Lahat H, Bakhan T, et al. Hypotrichosis simplex of the scalp is associated with nonsense mutations in CDSN encoding corneodesmosin. Nat Genet. 2003;34:151–3.
  • Oji V, Eckl KM, Aufenvenne K, Natebus M, Tarinski T, Ackermann K, et al. Loss of corneodesmosin leads to severe skin barrier defect, pruritus, and atopy: unraveling the peeling skin disease. Am J Hum Genet. 2010;87:274–81.
  • Sterk LM, Geuijen CA, Oomen LC, Calafat J, Janssen H, Sonnenberg A. The tetraspan molecule CD151, a novel constituent of hemidesmosomes, associates with the integrin alpha6beta4 and may regulate the spatial organization of hemidesmosomes. J Cell Biol. 2000;149:969–82.
  • Kagan A, Feld S, Chemke J, Bar-Khayim Y. Occurrence of hereditary nephritis, pretibial epidermolysis bullosa and beta-thalassemia minor in two siblings with end-stage renal disease. Nephron. 1988;49:331–2.
  • Karamatic Crew V, Burton N, Kagan A, Green CA, Levene C, Flinter F, et al. CD151, the first member of the tetraspanin (TM4) superfamily detected on erythrocytes, is essential for the correct assembly of human basement membranes in kidney and skin. Blood. 2004;104: 2217–23.
  • Arin MJ, Oji V, Emmert S, Hausser I, Traupe H, Krieg T, et al. Expanding the keratin mutation database: novel and recurrent mutations and genotype-phenotype correlations in 28 patients with epidermolytic ichthyosis. Br J Dermatol. 2011;164:442–7.
  • Oji V, Tadini G, Akiyama M, Blanchet Bardon C, Bodemer C, Bourrat E, et al. Revised nomenclature and classification of Soreze 2009. inherited ichthyoses: results of the First Ichthyosis Consensus Conference in J Am Acad Dermatol. 2010;63:607–41.
  • Varki R, Sadowski S, Uitto J, Pfendner E. Epidermolysis bullosa. II. Type VII collagen mutations and phenotype-genotype correlations in the dystrophic subtypes. J Med Genet. 2007;44:181–92.
  • Fassihi H, Eady RA, Mellerio JE, Ashton GH, Dopping-Hepenstal PJ, Denyer JE, et al. Prenatal diagnosis for severe inherited skin disorders: 25 years’ experience. Br J Dermatol. 2006;154:106–13.
  • Fassihi H, Liu L, Renwick PJ, Braude PR, McGrath JA. Development and successful clinical application of preimplantation genetic haplotyping for Herlitz junctional epidermolysis bullosa. Br J Dermatol. 2010;162:1330–6.
  • Leachman SA, Hickerson RP, Schwartz ME, Bullough EE, Hutcherson SL, Boucher KM, et al. First-in-human mutation-targeted siRNA phase Ib trial of an inherited skin disorder. Mol Ther. 2010; 18:442–6.
  • Atkinson SD, McGilligan VE, Liao H, Szeverenyi I, Smith FJ, Moore CB, et al. Development of allele-specific therapeutic siRNA for keratin 5 mutations in epidermolysis bullosa simplex. J Invest Dermatol. 2011;131:2079–86.
  • Wally V, Klausegger A, Koller U, Lochmuller H, Krause S, Wiche G, et al. 5’ Trans-splicing repair of the PLEC1 gene. J Invest Dermatol. 2008;128:568–74.
  • Dallinger G, Puttaraju M, Mitchell LG, Yancey KB, Yee C, Klausegger A, et al. Development of spliceosome-mediated RNA trans-splicing (SMaRT) for the correction of inherited skin diseases. Exp Dermatol. 2003;12:37–46.
  • Wally V, Brunner M, Lettner T, Wagner M, Koller U, Trost A, et al. K14 mRNA reprogramming for dominant epidermolysis bullosa simplex. Hum Mol Genet. 2010;19:4715–25.
  • Carulli S, Contin R, De Rosa L, Pellegrini G, De Luca M. The long and winding road that leads to a cure for epidermolysis bullosa. Regen Med. 2013;8:467–81.
  • Mavilio F, Pellegrini G, Ferrari S, Di Nunzio F, Di Iorio E, Recchia A, et al. Correction of junctional epidermolysis bullosa by transplantation of genetically modified epidermal stem cells. Nat Med. 2006;12: 1397–402.
  • Urnov FD, Rebar EJ, Holmes MC, Zhang HS, Gregory PD. Genome editing with engineered zinc finger nucleases. Nat Rev Genet. 2010; 11:636–46.
  • Carroll D. Genome engineering with zinc-finger nucleases. Genetics. 2011;188:773–82.
  • Osborn MJ, Starker CG, McElroy AN, Webber BR, Riddle MJ, Xia L, et al. TALEN-based gene correction for epidermolysis bullosa. Mol Ther. 2013;21:1151–9.
  • Remington J, Wang X, Hou Y, Zhou H, Burnett J, Muirhead T, et al. Injection of recombinant human type VII collagen corrects the disease phenotype in a murine model of dystrophic epidermolysis bullosa. Mol Ther. 2009;17:26–33.
  • Woodley DT, Wang X, Amir M, Hwang B, Remington J, Hou Y, et al. Intravenously injected recombinant human type VII collagen homes to skin wounds and restores skin integrity of dystrophic epidermolysis bullosa. J Invest Dermatol. 2013;133:1910–13.
  • Palazzi X, Marchal T, Chabanne L, Spadafora A, Magnol JP, Meneguzzi G. Inherited dystrophic epidermolysis bullosa in inbred dogs: a spontaneous animal model for somatic gene therapy. J Invest Dermatol. 2000;115:135–7.
  • Cogan J, Wang XY, Hou YP, Khilili M, Woodley DT, Chen M. Epitope mapping of anti-type VII collagen antibodies in the patients with recessive dystrophic epidermolysis bullosa. J Invest Dermatol. 2013;133:S45.
  • Wong T, Gammon L, Liu L, Mellerio JE, Dopping-Hepenstal PJ, Pacy J, et al. Potential of fibroblast cell therapy for recessive dystrophic epidermolysis bullosa. J Invest Dermatol. 2008;128:2179–89.
  • Nagy N, Almaani N, Tanaka A, Lai-Cheong JE, Techanukul T, Mellerio JE, et al. HB-EGF induces COL7A1 expression in keratinocytes and fibroblasts: possible mechanism underlying allogeneic fibroblast therapy in recessive dystrophic epidermolysis Bullosa. J Invest Dermatol. 2011;131:1771–4.
  • Fritsch A, Loeckermann S, Kern JS, Braun A, Bosl MR, Bley TA, et al. A hypomorphic mouse model of dystrophic epidermolysis bullosa reveals mechanisms of disease and response to fibroblast therapy. J Clin Invest. 2008;118:1669–79.
  • Kern JS, Loeckermann S, Fritsch A, Hausser I, Roth W, Magin TM, et al. Mechanisms of fibroblast cell therapy for dystrophic epidermolysis bullosa: high stability of collagen VII favors long-term skin integrity. Mol Ther. 2009;17:1605–15.
  • Venugopal SS, Yan W, Frew JW, Cohn HI, Rhodes LM, Tran K, et al. A phase II randomized vehicle-controlled trial of intradermal allogeneic fibroblasts for recessive dystrophic epidermolysis bullosa. J Am Acad Dermatol. 2013;69:898–908.e7.
  • Petrof G, Martinez-Queipo M, Mellerio JE, Kemp P, McGrath JA. Fibroblast cell therapy enhances initial healing in recessive dystrophic epidermolysis bullosa wounds: results of a randomised, vehicle- controlled trial. Br J Dermatol. 2013;169:1025–33.
  • Conget P, Rodriguez F, Kramer S, Allers C, Simon V, Palisson F, et al. Replenishment of type VII collagen and re-epithelialization of chronically ulcerated skin after intradermal administration of allogeneic mesenchymal stromal cells in two patients with recessive dystrophic epidermolysis bullosa. Cytotherapy. 2010;12:429–31.
  • Tamai K, Yamazaki T, Chino T, Ishii M, Otsuru S, Kikuchi Y, et al. PDGFRalpha-positive cells in bone marrow are mobilized by high mobility group box 1 (HMGB1) to regenerate injured epithelia. Proc Natl Acad Sci U S A. 2011;108:6609–14.
  • Dimarino AM, Caplan AI, Bonfield TL. Mesenchymal stem cells in tissue repair. Front Immunol. 2013;4:201.
  • Tolar J, Mehta PA, Walters MC. Hematopoietic cell transplantation for nonmalignant disorders. Biol Blood Marrow Transplant. 2012;18: S166–71.
  • Wagner JE, Ishida-Yamamoto A, McGrath JA, Hordinsky M, Keene DR, Woodley DT, et al. Bone marrow transplantation for recessive dystrophic epidermolysis bullosa. N Engl J Med. 2010;363:629–39.
  • Tolar J, Blazar BR, Wagner JE. Concise review: transplantation of human hematopoietic cells for extracellular matrix protein deficiency in epidermolysis bullosa. Stem Cells. 2011;29:900–6.
  • Tolar J, Wagner JE. Allogeneic blood and bone marrow cells for the treatment of severe epidermolysis bullosa: repair of the extracellular matrix. Lancet. 2013;382:1214–23.
  • Jonkman MF, Scheffer H, Stulp R, Pas HH, Nijenhuis M, Heeres K, et al. Revertant mosaicism in epidermolysis bullosa caused by mitotic gene conversion. Cell. 1997;88:543–51.
  • Almaani N, Nagy N, Liu L, Dopping-Hepenstal PJ, Lai-Cheong JE, Clements SE, et al. Revertant mosaicism in recessive dystrophic epidermolysis bullosa. J Invest Dermatol. 2010;130:1937–40.
  • Lai-Cheong JE, McGrath JA. Revertant mosaicism in the skin. G Ital Dermatol Venereol. 2013;148:73–82.
  • Pasmooij AM, Nijenhuis M, Brander R, Jonkman MF. Natural gene therapy may occur in all patients with generalized non-Herlitz junctional epidermolysis bullosa with COL17A1 mutations. J Invest Dermatol. 2012;132:1374–83.
  • Gostynski A, Deviaene FC, Pasmooij AM, Pas HH, Jonkman MF. Adhesive stripping to remove epidermis in junctional epidermolysis bullosa for revertant cell therapy. Br J Dermatol. 2009;161:444–7.
  • Gostynski A, Pasmooij AM, Bremer J, Huizinga J, Duipmans J, Jonkman MF. Successful therapeutic transplantation of revertant skin in a patient with epidermolysis bullosa. J Invest Dermatol. 2013; 133:S132.
  • Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131:861–72.
  • Hou P, Li Y, Liu C, Guan J, Li H, Zhao T, et al. Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds. Science.2013;341:651–4.
  • Tolar J, Xia L, Riddle MJ, Lees CJ, Eide CR, McElmurry RT, et al. Induced pluripotent stem cells from individuals with recessive dystrophic epidermolysis bullosa. J Invest Dermatol. 2011;131: 848–56.
  • Itoh M, Kiuru M, Cairo MS, Christiano AM. Generation of keratinocytes from normal and recessive dystrophic epidermolysis bullosa-induced pluripotent stem cells. Proc Natl Acad Sci U S A. 2011;108:8797–802.
  • Tolar J, McGrath JA, Xia L, Riddle M, Lees CJ, Eide C, et al. Patient-specific naturally gene-reverted induced pluripotent stem cells in recessive dystrophic epidermolysis bullosa. J Invest Dermatol. 2014; in press.
  • Bidou L, Allamand V, Rousset JP, Namy O. Sense from nonsense: therapies for premature stop codon diseases. Trends Mol Med. 2012;18:679–88.
  • Roberts RG. A read-through drug put through its paces. PLoS Biol. 2013;11:e1001458.
  • Zhou Y, Jiang Q, Takahagi S, Shao C, Uitto J. Premature termination codon read-through in the abcc6 gene: potential treatment for pseudoxanthoma elasticum. J Invest Dermatol. 2013;133:2672–7.
  • Wally V, Kitzmueller S, Lagler F, Moder A, Hitzl W, Wolkersdorfer M, et al. Topical diacerin for epidermolysis bullosa. Orphanet J Rare Dis. 2013;8:69.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.