Introduction

  • 1  Salam A, Proudfoot LE, McGrath JA. Inherited blistering skin diseases: underlying molecular mechanisms and emerging therapies. Ann Med 2014;46:49‐61. Cross Ref link Pubmed link

Definition and classification

  • 2  Koebner H. Hereditare anlage zur blasenbildung (epidermolysis bullosa hereditare). Dtsch Med Wochenschr 1886;12:21–2. Cross Ref link
  • 3  Pearson RW. Studies on the pathogenesis of epidermolysis bullosa. J Invest Dermatol 1962;39:551–75. Cross Ref link Pubmed link
  • 4  Fine J‐D, Bruckner‐Tuderman L, Eady RA, et al. Inherited epidermolysis bullosa: updated recommendations on diagnosis and classification. J Am Acad Dermatol 2014;70:1103‐26. Cross Ref link Pubmed link

Prevalence and incidence

  • 5  Fine J‐D, Johnson LB, Suchindran C, et al. The epidemiology of inherited epidermolysis bullosa: findings in the US, Canadian and European study populations. In: Fine J‐D, Bauer EA, McGuire J, Moshell A, eds. Clinical, Epidemiologic and Laboratory Advances and the Findings of the National Epidermolysis Bullosa Registry. Baltimore: Johns Hopkins University Press, 1999:101–13.

Skin proteins and genes implicated in epidermolysis bullosa

    Keratins 5 and 14: KRT5, KRT14

    • 6  Coulombe PA, Lee CH. Defining keratin protein function in skin epithelia: epidermolysis bullosa simplex and its aftermath. J Invest Dermatol 2012;132:763–75. Cross Ref link Pubmed link
    • 7  Sprecher E. Epidermolysis bullosa simplex. Dermatol Clin 2010;28:23–32. Cross Ref link Pubmed link

    Plakophilin‐1: PKP1

    • 8  McGrath JA, McMillan JR, Shemanko CS, et al. Mutations in the plakophilin 1 gene result in ectodermal dysplasia/skin fragility syndrome. Nat Genet 1997;17:240–4. Cross Ref link Pubmed link
    • 9  Kowalczyk AP, Green KJ. Structure, function, and regulation of desmosomes. Prog Mol Biol Transl Sci 2013;116:95–118. Cross Ref link Pubmed link

    Desmoplakin: DSP

    • 10  Armstrong DK, McKenna KE, Purkis PE, et al. Haploinsufficiency of desmoplakin causes a striate subtype of palmoplantar keratoderma. Hum Mol Genet 1999;8:143–8. Cross Ref link Pubmed link
    • 11  Jonkman MF, Pasmooij AM, Pasmans SG, et al. Loss of desmoplakin tail causes lethal acantholytic epidermolysis bullosa. Am J Hum Genet 2005;77:653–60. Cross Ref link Pubmed link

    Plakoglobin: JUP

    • 12  Yin T, Green KJ. Regulation of desmosome assembly and adhesion. Semin Cell Dev Biol 2004;15:665–77. Cross Ref link Pubmed link
    • 13  Cabral RM, Liu L, Hogan C, 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. Cross Ref link Pubmed link

    Exophilin‐5: EXPH5

    • 14  McGrath JA, Stone KL, Begum R, 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. Cross Ref link Pubmed link
    • 15  Stenmark H. Rab GTPases as coordinators of vesicle traffic. Nat Rev Mol Cell Biol 2009;10:513–25. Cross Ref link Pubmed link
    • 16  Pigors M, Schwieger‐Briel A, Leppert J, et al. Molecular heterogeneity of epidermolysis bullosa simplex: contribution of EXPH5 mutations. J Invest Dermatol 2014;134:842–5. Cross Ref link Pubmed link
    • 17  Liu L, Mellerio JE, Martinez AE, et al. Mutations in EXPH5 result in autosomal recessive inherited skin fragility. Br J Dermatol 2014;170:196–9. Cross Ref link Pubmed link

    Transglutaminase 5: TGM5

    • 18  Cassidy AJ, van Steensel MA, Steijlen PM, 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. Cross Ref link Pubmed link
    • 19  Kiritsi D, Cosgarea I, Franzke CW, 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. Cross Ref link Pubmed link

    Plectin: PLEC

    • 20  Winter L, Wiche G. The many faces of plectin and plectinopathies: pathology and mechanisms. Acta Neuropathol 2013;125:77–93. Cross Ref link Pubmed link
    • 21  Rezniczek GA, Walko G, Wiche G. Plectin gene defects lead to various forms of epidermolysis bullosa simplex. Dermatol Clin 2010;28:33–41. Cross Ref link Pubmed link
    • 22  Bolling MC, Jongbloed JD, Boven LG, et al. Plectin mutations underlie epidermolysis bullosa simplex in 8% of patients. J Invest Dermatol 2014;134(1):273–6. Cross Ref link Pubmed link

    Dystonin‐epidermal isoform (BP230): DST‐e

    • 23  Groves RW, Liu L, Dopping‐Hepenstal PJ, 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. Cross Ref link Pubmed link
    • 24  Michael M, Begum R, Fong K, et al. BPAG1‐e restricts keratinocyte migration through control of adhesion stability. J Invest Dermatol 2014;134:773–82. Cross Ref link Pubmed link

    α6β4 integrin: ITGA6, ITGB4

    • 25  Kligys KR, Wu Y, Hopkinson SB, et al. Alpha6beta4 integrin, a master regulator of expression of integrins in human keratinocytes. J Biol Chem 2012;287:17975–84. Cross Ref link Pubmed link
    • 26  Schumann H, Kiritsi D, Pigors M, et al. Phenotypic spectrum of epidermolysis bullosa associated with α6β4 integrin mutations. Br J Dermatol 2013;169:115–24. Cross Ref link Pubmed link

    α3 integrin subunit: ITGA3

    • 27  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. Cross Ref link Pubmed link
    • 28  Has C, Sparta G, Kiritsi D, et al. Integrin alpha3 mutations with kidney, lung, and skin disease. N Engl J Med 2012;366:1508–14. Cross Ref link Pubmed link

    Kindlin‐1: KIND1/FERMT1

    • 29  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. Cross Ref link Pubmed link
    • 30  Lai‐Cheong JE, Tanaka A, Hawche G, et al. Kindler syndrome: a focal adhesion genodermatosis. Br J Dermatol 2009;160:233–42. Cross Ref link Pubmed link

    Type XVII collagen: COL17A1

    • 31  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. Cross Ref link Pubmed link
    • 32  McGrath JA, Gatalica B, Christiano AM, 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. Cross Ref link Pubmed link

    Laminin‐332: LAMA3, LAMB3, LAMC2

    • 33  Kiritsi D, Has C, Bruckner‐Tuderman L. Laminin 332 in junctional epidermolysis bullosa. Cell Adh Migr 2013;7:135–41. Cross Ref link Pubmed link
    • 34  McLean WH, Irvine AD, Hamill KJ, 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. Cross Ref link Pubmed link

    Type VII collagen: COL7A1

    • 35  Burgeson RE, Lunstrum GP, Rokosova B, et al. The structure and function of type VII collagen. Ann NY Acad Sci 1990;580:32–43. Cross Ref link Pubmed link
    • 36  Chung HJ, Uitto J. Type VII collagen: the anchoring fibril protein at fault in dystrophic epidermolysis bullosa. Dermatol Clin 2010;28:93–105. Cross Ref link Pubmed link

    Other proteins and genes linked to skin fragility

      Desmocollin 3: DSC3

      • 37  Chen J, Den Z, Koch PJ. Loss of desmocollin 3 in mice leads to epidermal blistering. J Cell Sci 2008;121:2844–9. Cross Ref link Pubmed link
      • 38  Ayub M, Basit S, Jelani M, et al. A homoztgous nonsense mutation in the human desmocollin‐3 (DSC3) gene underlies hereditary hypotrichosis and recurrent skin vesicles. Am J Hum Genet 2009;85:515–20. Cross Ref link Pubmed link

      Desmoglein‐1: DSG1

      • 39  Amagai M, Stanley JR. Desmoglein as a target in skin disease and beyond. J Invest Dermatol 2012;132:776–84. Cross Ref link Pubmed link
      • 40  Samuelov L, Sarig O, Harmon RM, et al. Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting. Nat Genet 2013;45:1244–8. Cross Ref link Pubmed link

      Corneodesmosin: CDSN

      • 41  Levy‐Nissenbaum E, Betz RC, Frydman M, et al. Hypotrichosis simplex of the scalp is associated with nonsense mutations in CDSN encoding corneodesmosin. Nat Genet 2003;34:151–3. Cross Ref link Pubmed link
      • 42  Oji V, Eckl KM, Aufenvenne 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. Cross Ref link Pubmed link

      CD151 antigen/tetraspanin: CD151

      • 43  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. Cross Ref link Pubmed link
      • 44  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. Cross Ref link Pubmed link

      Keratins 1 and 10: KRT1, KRT10

      • 45  Arin MJ, Oji V, Emmert S, 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. Cross Ref link Pubmed link
      • 46  Oji V, Tadini G, Akiyama M, et al. Revised nomenclature and classification of inherited ichthyoses: results of the First Ichthyosis Consensus Conference in Soreze 2009. J Am Acad Dermatol 2010;63:607–41. Cross Ref link Pubmed link

      Clinical subtypes

        EB simplex

          Localized EB simplex
          • 47  Sprecher E. Epidermolysis bullosa simplex. Dermatol Clin 2010;28:23–32. Cross Ref link Pubmed link
          • 48  Coulombe PA, Kerns ML, Fuchs E. Epidermolysis bullosa simplex: a paradigm for disorders of tissue fragility. J Clin Invest 2009;119:1784–93. Cross Ref link Pubmed link
          Acral peeling skin syndrome
          • 49  Kiritsi D, Cosgarea I, Franzke CW, 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. Cross Ref link Pubmed link
          • 50  Van der Velden JJ, Jonkman MF, McLean WH, et al. A recurrent mutation in the TGM5 gene in European patients with acral peeling skin syndrome. J Dermatol Sci 2012;65:74–6. Cross Ref link Pubmed link
          Generalized severe EB simplex
          • 51  McGrath JA, Ishida‐Yamamoto A, Tidman MJ, et al. Epidermolysis bullosa simplex (Dowling–Meara). A clinicopathological review. Br J Dermatol 1992;126:421–30. Cross Ref link Pubmed link
          • 52  Haines RL, Lane EB. Keratins and disease at a glance. J Cell Sci 2012;125:3923–8. Cross Ref link Pubmed link
          Generalized intermediate EB simplex
          • 53  Ito M, Okuda C, Shimizu N, Tazawa T, Sato Y. Epidermolysis bullosa simplex (Koebner) is a keratin disorder. Ultrastructural and immunohistochemical study. Arch Dermatol 1991;127:367–72. Cross Ref link Pubmed link
          • 54  Rugg EL, Leigh IM. The keratins and their disorders. Am J Med Genet C Semin Med Genet 2004;131C:4–11. Cross Ref link Pubmed link
          EB simplex with mottled pigmentation
          • 55  Browning JC, Mohr B. Epidermolysis bullosa simplex with mottled pigmentation. Dermatol Online J 2012;18:9. Pubmed link
          • 56  Uttam J, Hutton E, Coulombe PA, et al. The genetic basis of epidermolysis bullosa simplex with mottled pigmentation. Proc Natl Acad Sci USA 1996;93:9079–84. Cross Ref link Pubmed link
          EB simplex Ogna
          • 57  Koss‐Harnes D, Høyheim B, Anton‐Lamprecht I, et al. A site‐specific plectin mutation causes dominant epidermolysis bullosa simplex Ogna: two identical de novo mutations. J Invest Dermatol 2002;118:87–93. Cross Ref link Pubmed link
          • 58  Kiritsi D, Pigors M, Tantcheva‐Poor I, et al. Epidermolysis bullosa simplex ogna revisited. J Invest Dermatol 2013;133:270–3. Cross Ref link Pubmed link
          EB simplex migratory circinate
          • 59  Gu L‐H, Kim S‐C, Ichiki Y, et al. A usual frameshift and delayed termination codon mutation in keratin 5 causes a novel type of epidermolysis bullosa simplex with migratory circinate erythema. J Invest Dermatol 2003;121:482–5. Cross Ref link Pubmed link
          • 60  Castiglia D, El Hachem M, Diociaiuti A, et al. T‐lymphocytes are directly involved in the clinical expression of migratory circinate erythema in epidermolysis bullosa simplex patients. Acta Derm Venereol 2014;94:307–11. Cross Ref link Pubmed link
          EB simplex autosomal recessive keratin 14
          • 61  Chan Y, Anton‐Lamprecht I, Yu QC, et al. A human keratin 14 “knockout”: the absence of K14 leads to severe epidermolysis bullosa simplex and a function for an intermediate filament protein. Genes Dev 1994;8:2574–87. Cross Ref link Pubmed link
          • 62  Yiasemides E, Trisnowati N, Su J, et al. Clinical heterogeneity in recessive epidermolysis bullosa due to mutations in the keratin 14 gene, KRT14. Clin Exp Dermatol 2008;33:689–97. Cross Ref link Pubmed link
          EB simplex with muscular dystrophy
          • 63  Uitto J, Pulkkinen L, Smith FJ, McLean WH. Plectin and human genetic disorders of the skin and muscle. The paradigm of epidermolysis bullosa with muscular dystrophy. Exp Dermatol 1996;5:237–46. Cross Ref link Pubmed link
          • 64  Mellerio JE, Smith FJ, McMillan JR, et al. Recessive epidermolysis bullosa simplex associated with plectin mutations: infantile respiratory complications in two unrelated cases. Br J Dermatol 1997;137:898–906. Cross Ref link Pubmed link
          EB simplex with pyloric atresia
          • 65  Nakamura H, Sawamura D, Goto M, et al. Epidermolysis bullosa simplex associated with pyloric atresia is a novel clinical subtype caused by mutations in the zplectin gene (PLEC1). J Mol Diagn 2005;7:28–35. Cross Ref link Pubmed link
          • 66  Natsuga K, Nishie W, Shinkuma S, et al. Plectin deficiency leads to both muscular dystrophy and pyloric atresia in epidermolysis bullosa simplex. Hum Mutat 2010;31:E1687–98. Cross Ref link Pubmed link
          EB simplex autosomal recessive BP230
          • 67  Groves RW, Liu L, Dopping‐Hepenstal PJ, 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 Cross Ref link Pubmed link
          • 68  Liu L, Dopping‐Hepenstal PJ, Lovell PA, et al. Autosomal recessive epidermolysis bullosa simplex due to loss of BPAG1‐e expression. J Invest Dermatol 2012;132:742–4. Cross Ref link Pubmed link
          EB simplex autosomal recessive exophilin‐5
          • 69  McGrath JA, Stone KL, Begum R, 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. Cross Ref link Pubmed link
          • 70  Pigors M, Schwieger‐Briel A, Leppert J, et al. Molecular heterogeneity of epidermolysis bullosa simplex: contribution of EXPH5 mutations. J Invest Dermatol 2014;134:842–5. Cross Ref link Pubmed link
          EB simplex plakophilin‐1 deficiency
          • 71  McGrath JA, McMillan JR, Shemanko CS, et al. Mutations in the plakophilin 1 gene result in ectodermal dysplasia/skin fragility syndrome. Nat Genet 1997;17:240–4. Cross Ref link Pubmed link
          • 72  McGrath JA, Mellerio JE. Ectodermal dysplasia–skin fragility syndrome. Dermatol Clin 2010;28:125–9. Cross Ref link Pubmed link
          EB simplex desmoplakin deficiency
          • 73  Jonkman MF, Pasmooij AM, Pasmans SG, et al. Loss of desmoplakin tail causes lethal acantholytic epidermolysis bullosa. Am J Hum Genet 2005;77:653–60. Cross Ref link Pubmed link
          • 74  Bolling MC, Veenstra MJ, Jonkman MF, et al. Lethal acantholytic epidermolysis bullosa due to a novel homozygous deletion in DSP: expanding the phenotype and implications for desmoplakin function in skin and heart. Br J Dermatol 2010;162:1388–94. Cross Ref link Pubmed link
          EB simplex plakoglobin deficiency
          • 75  Pigors M, Kiritsi D, Krümpelmann S, et al. Lack of plakoglobin leads to lethal congenital epidermolysis bullosa: a novel clinico‐genetic entity. Hum Mol Genet 2011;20:1811–9. Cross Ref link Pubmed link
          • 76  Petrof G, Mellerio JE, McGrath JA. Desmosomal genodermatoses. Br J Dermatol 2012;166:36–45. Cross Ref link Pubmed link
          EB simplex superficialis
          • 77  Fine JD, Johnson L, Wright T. Epidermolysis bullosa simplex superficialis. A new variant of epidermolysis bullosa characterized by subcorneal skin cleavage mimicking peeling skin syndrome. Arch Dermatol 1989;125:633–8. Cross Ref link Pubmed link
          • 78  Martinez‐Mir A, Liu J, Gordon D, et al. EB simplex superficialis resulting from a mutation in the type VII collagen gene. J Invest Dermatol 2002;118:547–9. Cross Ref link Pubmed link

          Junctional EB

            Generalized severe junctional EB
            • 79  Laimer M, Lanschuetzer CM, Diem A, Bauer JW. Herlitz junctional epidermolysis bullosa. Dermatol Clin 2010;28:55–60. Cross Ref link Pubmed link
            • 80  Yuen WY, Lemmink HH, van Dijk‐Bos KK, et al. Herlitz junctional epidermolysis bullosa: diagnostic features, mutational profile, incidence and population carrier frequency in the Netherlands. Br J Dermatol 2011;165:1314–22. Cross Ref link Pubmed link
            Generalized intermediate junctional EB
            • 81  Yancey KB, Hintner H. Non‐herlitz junctional epidermolysis bullosa. Dermatol Clin 2010;28:67–77. Cross Ref link Pubmed link
            • 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. Cross Ref link Pubmed link
            Generalized late‐onset junctional EB
            • 83  Stouthamer A, Nieboer C, van der Waal RI, Jonkman MF. Normal expression of the 19‐DEJ‐1 epitope in two siblings with late‐onset junctional epidermolysis bullosa. Br J Dermatol 2001;144:1054–7. Cross Ref link Pubmed link
            • 84  Yuen WY, Pas HH, Sinke RJ, Jonkman MF. Junctional epidermolysis bullosa of late onset explained by mutations in COL17A1. Br J Dermatol 2011;164:1280–4. Cross Ref link Pubmed link
            Junctional EB with pyloric atresia
            • 85  Ashton GH, Sorelli P, Mellerio JE, et al. Alpha 6 beta 4 integrin abnormalities in junctional epidermolysis bullosa with pyloric atresia. Br J Dermatol 2001;144:408–14. Cross Ref link Pubmed link
            • 86  Schumann H, Kiritsi D, Pigors M, et al. Phenotypic spectrum of epidermolysis bullosa associated with α6β4 integrin mutations. Br J Dermatol 2013;169:115–24. Cross Ref link Pubmed link
            Junctional EB with respiratory and renal involvement
            • 87  Has C, Sparta G, Kiritsi D, et al. Integrin alpha3 mutations with kidney, lung, and skin disease. N Engl J Med 2012;366:1508–14. Cross Ref link Pubmed link
            • 88  Shukrun R, Vivante A, Pleniceanu O, et al. A human integrin‐α3 mutation confers major renal developmental defects. PLOS One 2014;9:e90879. Cross Ref link Pubmed link
            Localized junctional EB
            • 89  Floeth M, Fiedorowicz J, Schäcke H, et al. Novel homozygous and compound heterozygous COL17A1 mutations associated with junctional epidermolysis bullosa. J Invest Dermatol 1998;111:528–33. Cross Ref link Pubmed link
            • 90  Pasmooij AM, Pas HH, Jansen GH, et al. Localized and generalized forms of blistering in junctional epidermolysis bullosa due to COL17A1 mutations in the Netherlands. Br J Dermatol 2007;156:861–70. Cross Ref link Pubmed link
            Localized junctional EB inversa
            • 91  Ridley CM. Epidermolysis bullosa with unusual features: inversa type. Proc R Soc Med 1977;70:576–7. Pubmed link
            • 92  Gedde‐Dahl T, Jr, Dupuy BM, Jonassen R, et al. Junctional epidermolysis bullosa inversa (locus EBR2A) assigned to 1q31 by linkage and association to LAMC1. Hum Mol Genet 1994;3:1387–91. Cross Ref link Pubmed link
            Localized junctional EB laryngo‐onycho‐cutaneous syndrome
            • 93  McLean WH, Irvine AD, Hamill KJ, 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. Cross Ref link Pubmed link
            • 94  Barzegar M, Mozafari N, Kariminejad A, et al. A new homozygous nonsense mutation in LAMA3A underlying laryngo‐onycho‐cutaneous syndrome. Br J Dermatol 2013;169:1353–6. Cross Ref link Pubmed link

            Dystrophic EB

              Dominant dystrophic EB generalized
              • 95  Fortuna G, Di Lorenzo M, Cepeda‐Valdes R, et al. The largest family of the Americas with dominant dystrophic epidermolysis bullosa pruriginosa: a 18‐year longitudinal genotype‐phenotype study. J Dermatol Sci 2013;71:217–21. Cross Ref link Pubmed link
              • 96  Christiano AM, Bart BJ, Epstein EH, Jr, Uitto J. Genetic basis of Bart's syndrome: a glycine substitution mutation in the type VII collagen gene. J Invest Dermatol 1996;106:1340–2. Cross Ref link Pubmed link
              Dominant dystrophic EB acral
              • 97  Cserhalmi‐Friedman PB, Grossman J, Karpati S, et al. Identification of a de novo glycine substitution in the type VII collagen gene in a proband with mild dystrophic epidermolysis bullosa. Exp Dermatol 1999;8:143–5. Cross Ref link Pubmed link
              • 98  Fine J‐D, Bruckner‐Tuderman L, Eady RA, et al. Inherited epidermolysis bullosa: updated recommendations on diagnosis and classification. J Am Acad Dermatol 2014;70:1103–26. Cross Ref link Pubmed link
              Dominant or recessive dystrophic EB pretibial
              • 99  Kuske H. Epidermolysis traumatica: regionar uber beiden Tibiae zur Atrophie fuhrend mit dominanter Vererbung. Dermatologica 1946;91:304–5.
              • 100  Lee JY, Chen HC, Lin SJ. Pretibial epidermolysis bullosa: a clinicopathologic study. J Am Acad Dermatol 1993;29:974–81. Cross Ref link Pubmed link
              Dominant or recessive dystrophic EB pruriginosa
              • 101  McGrath JA, Schofield OM, Eady RA. Epidermolysis bullosa pruriginosa: dystrophic epidermolysis bullosa with distinctive clinicopathological features. Br J Dermatol 1994;130:617–25. Cross Ref link Pubmed link
              • 102  Mellerio JE, Ashton GH, Mohammedi R, et al. Allelic heterogeneity of dominant and recessive COL7A1 mutations underlying epidermolysis bullosa pruriginosa. J Invest Dermatol 1999;112:984–7. Cross Ref link Pubmed link
              Dominant dystrophic EB nails only
              • 103  Dharma B, Moss C, McGrath JA, et al. Dominant dystrophic epidermolysis bullosa presenting as familial nail dystrophy. Clin Exp Dermatol 2001;26:93–6. Pubmed link
              • 104  Tosti A, Piraccini BM, Scher RK. Isolated nail dystrophy suggestive of dominant dystrophic epidermolysis bullosa. Pediatr Dermatol 2003;20:456–7. Cross Ref link Pubmed link
              Dominant or recessive dystrophic bullous dermolysis of the newborn
              • 105  Hashimoto K, Matsumoto M, Iacobelli D. Transient bullous dermolysis of the newborn. Arch Dermatol 1985;121:1429–38. Cross Ref link Pubmed link
              • 106  Radkevich‐Brown O, Shwayder T. Bullous dermolysis of the newborn: four new cases and clinical review. Pediatr Dermatol 2013;30:736–40. Cross Ref link Pubmed link
              Recessive dystrophic EB generalized severe
              • 107  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. Cross Ref link Pubmed link
              • 108  Fine JD, Mellerio JE. Extracutaneous manifestations and complications of inherited epidermolysis bullosa: part II. Other organs. J Am Acad Dermatol 2009;61:387–402. Cross Ref link Pubmed link
              Recessive dystrophic EB generalized intermediate
              • 109  Uitto J, Richard G. Progress in epidermolysis bullosa: genetic classification and clinical implications. Am J Med Genet C Semin Med Genet 2004;131C:61–74. Cross Ref link Pubmed link
              • 110  Bruckner‐Tuderman L. Dystrophic epidermolysis bullosa: pathogenesis and clinical features. Dermatol Clin 2010;28:107–14. Cross Ref link Pubmed link
              Recessive dystrophic EB inversa
              • 111  Pearson RW, Paller AS. Dermolytic (dystrophic) epidermolysis bullosa inversa. Arch Dermatol 1988;124:544–7. Cross Ref link Pubmed link
              • 112  Van den Akker PC, Mellerio JE, Martinez AE, et al. The inversa type of recessive dystrophic epidermolysis bullosa is caused by specific arginine and glycine substitutions in type VII collagen. J Med Genet 2011;48:160–7. Cross Ref link Pubmed link
              Recessive dystrophic EB localized
              • 113  Horn HM, Tidman MJ. The clinical spectrum of dystrophic epidermolysis bullosa. Br J Dermatol 2002;146:267–74. Cross Ref link Pubmed link
              • 114  Von Bartenwerffer W, Has C, Arin MJ, et al. Mild recessive dystrophic epidermolysis bullosa associated with two compound heterozygous COL7A1 mutations. Eur J Dermatol 2011;21:170–2 Pubmed link
              Recessive dystrophic EB centripetalis
              • 115  Fine J‐D, Bruckner‐Tuderman L, Eady RA, et al. Inherited epidermolysis bullosa: updated recommendations on diagnosis and classification. J Am Acad Dermatol 2014;70:1103–26. Cross Ref link Pubmed link
              • 116  Fine J‐D, Osment LS, Gay S. Dystrophic epidermolysis bullosa: a new variant characterized by progressive symmetrical centripetal involvement with scarring. Arch Dermatol 1985;121:1014–17. Cross Ref link Pubmed link

              Kindler syndrome

              • 117  Ashton GH. Kindler syndrome. Clin Exp Dermatol 2004;29:116–21. Cross Ref link Pubmed link
              • 118  Lai‐Cheong JE, Tanaka A, Hawche G, et al. Kindler syndrome: a focal adhesion genodermatosis. Br J Dermatol 2009;160:233–42. Cross Ref link Pubmed link

              Molecular pathology of Kindler syndrome

              • 119  Jobard F, Bouadjar B, Caux 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. Cross Ref link Pubmed link
              • 120  Siegel DH, Ashton GH, Penagos HG, 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. Cross Ref link Pubmed link

              Diagnosis

                Skin biopsy

                • 121  Intong LR, Murrell DF. Inherited epidermolysis bullosa: new diagnostic criteria and classification. Clin Dermatol 2012;30:70–7. Cross Ref link Pubmed link
                • 122  Vaughan Jones SA, Palmer I, Bhogal BS, et al. The use of Michel's transport medium for immunofluorescence and immunoelectron microscopy in autoimmune bullous diseases. J Cutan Pathol 1995;22:365–70. Cross Ref link Pubmed link

                Transmission electron microscopy

                • 123  Eady RAJ, Tidman MJ. Diagnosing epidermolysis bullosa. Br J Dermatol 1983;108 621–6. Cross Ref link Pubmed link
                • 124  Shinkuma S, McMillan JR, Shimizu H. Ultrastructure and molecular pathogenesis of epidermolysis bullosa. Clin Dermatol 2011;29:412–19. Cross Ref link Pubmed link

                Antigen mapping and antibody probes

                • 125  Pohla‐Gubo G, Cepeda‐Valdes R, Hintner H. Immunofluorescence mapping for the diagnosis of epidermolysis bullosa. Dermatol Clin 2010;28:201–10. Cross Ref link Pubmed link
                • 126  McGrath JA, Eady RA. The role of immunohistochemistry in the diagnosis of the non‐lethal forms of junctional epidermolysis bullosa. J Dermatol Sci 1997;14:68–75. Cross Ref link Pubmed link

                Sanger sequencing

                • 127  Castiglia D, Zambruno G. Molecular testing in epidermolysis bullosa. Dermatol Clin 2010;28:223–9. Cross Ref link Pubmed link
                • 128  Christiano AM, Hoffman GG, Zhang X, et al. Strategy for identification of sequence variants in COL7A1 and a novel 2‐bp deletion mutation in recessive dystrophic epidermolysis bullosa. Hum Mutat 1997;10:408–14. Cross Ref link Pubmed link

                Next generation sequencing

                • 129  Cho RJ, Simpson MA, McGrath JA. Next‐generation diagnostics for genodermatoses. J Invest Dermatol 2012;132:E27–8. Pubmed link
                • 130  Takeichi T, Nanda A, Liu L, et al. Impact of next generation sequencing on diagnostics in a genetic skin disease clinic. Exp Dermatol 2013;22:825–31. Cross Ref link Pubmed link

                Differential diagnosis

                • 131  Intong LR, Murrell DF. Inherited epidermolysis bullosa: new diagnostic criteria and classification. Clin Dermatol 2012;30:70–7. Cross Ref link Pubmed link
                • 132  Kiritsi D, Cosgarea I, Franzke CW, 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 Cross Ref link Pubmed link

                Other blistering genodermatoses

                  Peeling skin syndromes

                  • 133  Krunic AL, Stone KL, Simpson MA, McGrath JA. Acral peeling skin syndrome resulting from a homozygous nonsense mutation in the CSTA gene encoding cystatin A. Pediatr Dermatol 2013;30:e87–8. Cross Ref link Pubmed link
                  • 134  Blaydon DC, Nitoiu D, Eckl KM, et al. Mutations in CSTA, encoding Cystatin A, underlie exfoliative ichthyosis and reveal a role for this protease inhibitor in cell–cell adhesion. Am J Hum Genet 2011 89:564–71. Cross Ref link Pubmed link
                  • 135  Cabral RM, Kurban M, Wajid M, et al. Whole‐exome sequencing in a single proband reveals a mutation in the CHST8 gene in autosomal recessive peeling skin syndrome. Genomics 2012;99:202–8. Cross Ref link Pubmed link
                  • 136  Oji V, Eckl KM, Aufenvenne 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. Cross Ref link Pubmed link
                  • 137  Samuelov L, Sarig O, Harmon RM, et al. Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting. Nat Genet 2013;45:1244–8. Cross Ref link Pubmed link

                  Keratodermas

                  • 138  Kimonis V, DiGiovanna JJ, Yang JM, et al. A mutation in the V1 end domain of keratin 1 in non‐epidermolytic palmar‐plantar keratoderma. J Invest Dermatol 1994;103:764–9. Cross Ref link Pubmed link
                  • 139  Reis A, Hennies HC, Langbein L, et al. Keratin 9 gene mutations in epidermolytic palmoplantar keratoderma (EPPK). Nat Genet 1994;6:174–9. Cross Ref link Pubmed link
                  • 140  McLean WH, Rugg EL, Lunny DP, et al. Keratin 16 and keratin 17 mutations cause pachyonychia congenita. Nat Genet 1995;9:273–8. Cross Ref link Pubmed link
                  • 141  Blaydon DC, Lind LK, Plagnol V, et al. Mutations in AQP5, encoding a water‐channel protein, cause autosomal‐dominant diffuse nonepidermolytic palmoplantar keratoderma. Am J Hum Genet 2013;93:330–5. Cross Ref link Pubmed link

                  Calcium pump disorders

                  • 142  Sakuntabhai A, Ruiz‐Perez V, Carter S, et al. Mutations in ATP2A2, encoding a Ca2+ pump, cause Darier disease. Nat Genet 1999;21:271–7. Cross Ref link Pubmed link
                  • 143  Cooper SM, Burge SM. Darier's disease: epidemiology, pathophysiology, and management. Am J Clin Dermatol 2003;4:97–105. Cross Ref link Pubmed link
                  • 144  Hu Z, Bonifas JM, Beech J, et al. Mutations in ATP2C1, encoding a calcium pump, cause Hailey–Hailey disease. Nat Genet 2000;24:61–5. Cross Ref link Pubmed link
                  • 145  Dhitavat J, Fairclough RJ, Hovnanian A, Burge SM. Calcium pumps and keratinocytes: lessons from Darier's disease and Hailey–Hailey disease. Br J Dermatol 2004;150:821–8. Cross Ref link Pubmed link

                  Desmosomal disorders

                  • 146  Nitoiu D, Etheridge SL, Kelsell DP. Insights into desmosome biology from inherited human skin disease and cardiocutaneous syndromes. Cell Commun Adhes 2014;21:129–40. Cross Ref link Pubmed link
                  • 147  Petrof G, Mellerio JE, McGrath JA. Desmosomal genodermatoses. Br J Dermatol 2012;166:36–45. Cross Ref link Pubmed link

                  Metabolic and signalling disorders

                  • 148  Küry S, Dréno B, Bézieau S, et al. Identification of SLC39A4, a gene involved in acrodermatitis enteropathica. Nat Genet 2002;31:239–40. Cross Ref link Pubmed link
                  • 149  Smahi A, Courtois G, Rabia SH, et al. The NF‐kappaB signalling pathway in human diseases: from incontinentia pigmenti to ectodermal dysplasias and immune‐deficiency syndromes. Hum Mol Genet 2002;11:2371–5. Cross Ref link Pubmed link

                  Treatment

                    Management of neonates and infants

                    • 150  Denyer J. Management of severe blistering disorders. Semin Neonatol 2000;5:321–4. Cross Ref link Pubmed link
                    • 151  Mellerio JE, Weiner M, Denyer JE, et al. Medical management of epidermolysis bullosa: Proceedings of the IInd International Symposium on Epidermolysis Bullosa, Santiago, Chile, 2005. Int J Dermatol 2007;46:795–800. Cross Ref link Pubmed link

                    Management of EB simplex

                    • 152  Pope E, Lara‐Corrales I, Mellerio J, et al. A consensus approach to wound care in epidermolysis bullosa. J Am Acad Dermatol 2012;67:904–17. Cross Ref link Pubmed link
                    • 153  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. Cross Ref link Pubmed link

                    Management of generalized severe junctional EB

                    • 154  Yan EG, Paris JJ, Ahluwalia J, et al. Treatment decision‐making for patients with the Herlitz subtype of junctional epidermolysis bullosa. J Perinatol 2007;27:307–11. Cross Ref link Pubmed link
                    • 155  Fine JD, Johnson LB, Weiner M, Suchindran C. Tracheolaryngeal complications of inherited epidermolysis bullosa: cumulative experience of the national epidermolysis bullosa registry. Laryngoscope 2007;117:1652–60. Cross Ref link Pubmed link

                    Management of generalized severe recessive dystrophic EB

                      Oral and dental care

                      • 156  Kummer TR, Nagano HC, Tavares SS, et al. Oral manifestations and challenges in dental treatment of epidermolysis bullosa dystrophica. J Dent Child (Chic) 2013;80:97–100. Pubmed link
                      • 157  Sharma SM, Mohan M, Baptist J. Dental considerations in hereditary epidermolysis bullosa. NY State Dent J 2014;80:45–8.

                      Gastro‐intestinal tract and nutrition

                      • 158  Freeman EB, Köglmeier J, Martinez AE, et al. Gastrointestinal complications of epidermolysis bullosa in children. Br J Dermatol 2008;158:1308–14. Cross Ref link Pubmed link
                      • 159  Hubbard L, Haynes L, Sklar M, et al. The challenges of meeting nutritional requirements in children and adults with epidermolysis bullosa: proceedings of a multidisciplinary team study day. Clin Exp Dermatol 2011;36:579–83. Cross Ref link Pubmed link

                      Eyes

                      • 160  Fine JD, Johnson LB, Weiner M, et al. Eye involvement in inherited epidermolysis bullosa: experience of the National Epidermolysis Bullosa Registry. Am J Ophthalmol 2004;138:254–62. Cross Ref link Pubmed link
                      • 161  Figueira EC, Murrell DF, Coroneo MT. Ophthalmic involvement in inherited epidermolysis bullosa. Dermatol Clin 2010;28:143–52. Cross Ref link Pubmed link

                      Musculoskeletal system

                      • 162  Fine JD, Johnson LB, Weiner M, et al. Pseudosyndactyly and musculoskeletal contractures in inherited epidermolysis bullosa: experience of the National Epidermolysis Bullosa Registry, 1986–2002. J Hand Surg Br 2005;30:14–22. Cross Ref link Pubmed link
                      • 163  Fine JD, Mellerio JE. Extracutaneous manifestations and complications of inherited epidermolysis bullosa: part II. Other organs. J Am Acad Dermatol 2009;61:387–402. Cross Ref link Pubmed link

                      Anaemia

                      • 164  Hubbard L, Haynes L, Sklar M, et al. The challenges of meeting nutritional requirements in children and adults with epidermolysis bullosa: proceedings of a multidisciplinary team study day. Clin Exp Dermatol 2011;36:579–83. Cross Ref link Pubmed link
                      • 165  Atherton DJ, Cox I, Hann I. Intravenous iron (III) hydroxide–sucrose complex for anaemia in epidermolysis bullosa. Br J Dermatol 1999;140:773. Pubmed link

                      Bony abnormalities

                      • 166  Reyes ML, Cattani A, Gajardo H, et al. Bone metabolism in children with epidermolysis bullosa. J Pediatr 2002;140:467–9. Cross Ref link Pubmed link
                      • 167  Martinez AE, Mellerio JE. Osteopenia and osteoporosis in epidermolysis bullosa. Dermatol Clin 2010;28:353–5. Cross Ref link Pubmed link

                      Genito‐urinary tract abnormalities

                      • 168  Almaani N, Mellerio JE. Genitourinary tract involvement in epidermolysis bullosa. Dermatol Clin 2010;28:343–6. Cross Ref link Pubmed link
                      • 169  Burgu B, Duffy PG, Wilcox DT. Single‐centre experience of genitourinary complications of epidermolysis bullosa. J Pediatr Urol 2006;2:583–6. Cross Ref link Pubmed link

                      Systemic treatments for recessive dystrophic EB

                      • 170  Caldwell‐Brown D, Stern RS, Lin AN, Carter DM. Lack of efficacy of phenytoin in recessive dystrophic epidermolysis bullosa. Epidermolysis Bullosa Study Group. N Engl J Med 1992;327:163–7. Cross Ref link Pubmed link
                      • 171  Langan SM, Williams HC. A systematic review of randomized controlled trials of treatments for inherited forms of epidermolysis bullosa. Clin Exp Dermatol 2009;34:20–5. Cross Ref link Pubmed link

                      Cancer and recessive dystrophic EB

                      • 172  South AP, O'Toole EA. Understanding the pathogenesis of recessive dystrophic epidermolysis bullosa squamous cell carcinoma. Dermatol Clin 2010;28:171–8. Cross Ref link Pubmed link
                      • 173  Venugopal SS, Murrell DF. Treatment of skin cancers in epidermolysis bullosa. Dermatol Clin 2010;28:283–7. Cross Ref link Pubmed link

                      Pain management

                      • 174  Herod J, Denyer J, Goldman A, Howard R. Epidermolysis bullosa in children: pathophysiology, anaesthesia and pain management. Paediatr Anaesth 2002;12:388–97. Cross Ref link Pubmed link
                      • 175  Goldschneider KR, Lucky AW. Pain management in epidermolysis bullosa. Dermatol Clin 2010;28:273–82. Cross Ref link Pubmed link

                      Skin grafting

                      • 176  McGrath JA, Schofield OM, Ishida‐Yamamoto A, et al. Cultured keratinocyte allografts and wound healing in severe recessive dystrophic epidermolysis bullosa. J Am Acad Dermatol 1993;29:407–19. Cross Ref link Pubmed link
                      • 177  Natsuga K, Sawamura D, Goto M, et al. Response of intractable skin ulcers in recessive dystrophic epidermolysis bullosa patients to an allogeneic cultured dermal substitute. Acta Derm Venereol 2010;90:165–9. Cross Ref link Pubmed link

                      Innovative therapies

                      • 178  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. Cross Ref link Pubmed link

                      Gene therapy for dominant EB

                      • 179  Leachman SA, Hickerson RP, Schwartz ME, et al. First‐in‐human mutation‐targeted siRNA phase Ib trial of an inherited skin disorder. Mol Ther 2010;18:442–6. Cross Ref link Pubmed link
                      • 180  Bauer JW, Murauer EM, Wally V, Koller U. RNA trans‐splicing for genodermatoses. Methods Mol Biol 2013;961:441–55. Cross Ref link Pubmed link

                      Gene therapy for recessive EB

                      • 181  Mavilio F, Pellegrini G, Ferrari S, et al. Correction of junctional epidermolysis bullosa by transplantation of genetically modified epidermal stem cells. Nat Med 2006;12:1397–402. Cross Ref link Pubmed link
                      • 182  Cutlar L, Greiser U, Wang W. Gene therapy: pursuing restoration of dermal adhesion in recessive dystrophic epidermolysis bullosa. Exp Dermatol 2014;23:1–6. Cross Ref link Pubmed link

                      Genomic editing

                      • 183  Urnov FD, Rebar EJ, Holmes MC, et al. Genome editing with engineered zinc finger nucleases. Nat Rev Genet 2010;11:636–46. Cross Ref link Pubmed link
                      • 184  Osborn MJ, Starker CG, McElroy AN, et al. TALEN‐based gene correction for epidermolysis bullosa. Mol Ther 2013;211:151–9.

                      Recombinant protein therapy

                      • 185  Woodley DT, Wang X, Amir M, 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. Cross Ref link Pubmed link
                      • 186  Palazzi X, Marchal T, Chabanne L, et al. Inherited dystrophic epidermolysis bullosa in inbred dogs: a spontaneous animal model for somatic gene therapy. J Invest Dermatol 2000;115:135–7. Cross Ref link Pubmed link

                      Cell therapy with intradermal allogeneic fibroblasts

                      • 187  Nagy N, Almaani N, Tanaka A, 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. Cross Ref link Pubmed link
                      • 188  Venugopal SS, Yan W, Frew JW, 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. Cross Ref link Pubmed link
                      • 189  Petrof G, Martinez‐Queipo M, Mellerio JE, et al. 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. Cross Ref link Pubmed link

                      Cell therapy with intradermal mesenchymal stromal cells

                      • 190  Conget P, Rodriguez F, Kramer S, 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. Cross Ref link Pubmed link
                      • 191  Tamai K, Yamazaki T, Chino T, 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 USA 2011;108:6609–14. Cross Ref link Pubmed link

                      Bone marrow stem cell therapy

                      • 192  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. Cross Ref link Pubmed link
                      • 193  Wagner JE, Ishida‐Yamamoto A, McGrath JA, et al. Bone marrow transplantation for recessive dystrophic epidermolysis bullosa. N Engl J Med 2010;363:629–39. Cross Ref link Pubmed link

                      Natural gene therapy: revertant mosaicism

                      • 194  Jonkman MF, Scheffer H, Stulp R, et al. Revertant mosaicism in epidermolysis bullosa caused by mitotic gene conversion. Cell 1997;88:543–51. Cross Ref link Pubmed link
                      • 195  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. Cross Ref link Pubmed link
                      • 196  Gostyński A, Pasmooij AM, Jonkman MF. Successful therapeutic transplantation of revertant skin in epidermolysis bullosa. J Am Acad Dermatol 2014;70:98–101. Cross Ref link Pubmed link

                      Inducible pluripotent stem cells

                      • 197  Takahashi K, Tanabe K, Ohnuki M, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007;131:861–72. Cross Ref link Pubmed link
                      • 198  Tolar J, Xia L, Riddle MJ, et al. Induced pluripotent stem cells from individuals with recessive dystrophic epidermolysis bullosa. J Invest Dermatol 2011;131:848–56. Cross Ref link Pubmed link

                      Nonsense read‐through drugs and small molecule therapies

                      • 199  Bidou L, Allamand V, Rousset JP, Namy O. Sense from nonsense: therapies for premature stop codon diseases. Trends Mol Med 2012;18:679–88. Cross Ref link Pubmed link
                      • 200  Wally V, Kitzmueller S, Lagler F, et al. Topical diacerin for epidermolysis bullosa. Orphanet J Rare Dis 2013;8:69. Cross Ref link Pubmed link