Genomes and Genes
epidermolysis bullosa dystrophica
Summary: Form of epidermolysis bullosa characterized by atrophy of blistered areas, severe scarring, and nail changes. It is most often present at birth or in early infancy and occurs in both autosomal dominant and recessive forms. All forms of dystrophic epidermolysis bullosa result from mutations in COLLAGEN TYPE VII, a major component fibrils of BASEMENT MEMBRANE and EPIDERMIS.
- Hammami Hauasli N, Schumann H, Raghunath M, Kilgus O, Lüthi U, Luger T, et al. Some, but not all, glycine substitution mutations in COL7A1 result in intracellular accumulation of collagen VII, loss of anchoring fibrils, and skin blistering. J Biol Chem. 1998;273:19228-34 pubmed
- Petrova A, Ilic D, McGrath J. Stem cell therapies for recessive dystrophic epidermolysis bullosa. Br J Dermatol. 2010;163:1149-56 pubmed publisher..There is currently no single optimal therapy for patients with RDEB, but cell therapy technologies are evolving and hold great potential for modifying disease severity and improving quality of life for people living with RDEB. ..
- Pruneddu S, Castiglia D, Floriddia G, Cottoni F, Zambruno G. COL7A1 Recessive mutations in two siblings with distinct subtypes of dystrophic epidermolysis bullosa: pruriginosa versus nails only. Dermatology. 2011;222:10-4 pubmed publisher..Our findings document the rare occurrence of recessive inheritance for the nails only DEB variant and emphasize the role of acquired phenotype-modifying factors in DEB pruriginosa pathogenesis. ..
- Hovnanian A, Rochat A, Bodemer C, Petit E, Rivers C, Prost C, et al. Characterization of 18 new mutations in COL7A1 in recessive dystrophic epidermolysis bullosa provides evidence for distinct molecular mechanisms underlying defective anchoring fibril formation. Am J Hum Genet. 1997;61:599-610 pubmed..Genotype-phenotype correlations suggested that the nature and location of these mutations are important determinants of the disease phenotype and showed evidence for interfamilial phenotypic variability. ..
- Kern J, Kohlhase J, Bruckner Tuderman L, Has C. Expanding the COL7A1 mutation database: novel and recurrent mutations and unusual genotype-phenotype constellations in 41 patients with dystrophic epidermolysis bullosa. J Invest Dermatol. 2006;126:1006-12 pubmed..In addition, the studies disclosed a de novo mutation in recessive DEB and two new polymorphisms in the COL7A1 gene. ..
- Almaani N, Liu L, Dopping Hepenstal P, Lai Cheong J, Wong A, Nanda A, et al. Identical glycine substitution mutations in type VII collagen may underlie both dominant and recessive forms of dystrophic epidermolysis bullosa. Acta Derm Venereol. 2011;91:262-6 pubmed publisher..In screening the COL7A1 gene for mutations in individuals with DEB our data highlight that delineation of glycine substitutions in type VII collagen has important implications for genetic counselling. ..
- Hamada T, Fukuda S, Ishii N, Sakaguchi S, Ishikawa T, Abe T, et al. Genotype-phenotype correlation in non-Hallopeau-Siemens recessive dystrophic epidermolysis bullosa: the splice site mutation c.6216+5G > T in the COL7A1 gene results in aberrant and normal splicings. J Dermatol Sci. 2008;50:147-50 pubmed publisher
- Huang L, Wong Y, Burd A. A novel homozygous splice site mutation in COL7A1 in a Chinese patient with severe recessive dystrophic epidermolysis bullosa and squamous cell carcinoma. Int J Dermatol. 2011;50:52-6 pubmed publisher..This report contributes to the expanding database of COL7A1 mutations and emphasizes the need to elucidate the underlying genetic mechanisms associated with the increased incidence of SCC in RDEB patients. ..
- Bruckner Tuderman L. Dystrophic epidermolysis bullosa: pathogenesis and clinical features. Dermatol Clin. 2010;28:107-14 pubmed publisher..Potential therapies are in development. This article describes the pathogenesis and clinical features of DEB. It also describes therapeutic options and the future of molecular therapies. ..
- Ito K, Sawamura D, Goto M, Nakamura H, Nishie W, Sakai K, et al. Keratinocyte-/fibroblast-targeted rescue of Col7a1-disrupted mice and generation of an exact dystrophic epidermolysis bullosa model using a human COL7A1 mutation. Am J Pathol. 2009;175:2508-17 pubmed publisher..This model has great potential for future research into the pathomechanisms of dystrophic epidermolysis bullosa and the development of gene therapies for patients with dystrophic epidermolysis bullosa. ..
- Csikos M, Szocs H, Laszik A, Mecklenbeck S, Horvath A, Karpati S, et al. High frequency of the 425A-->G splice-site mutation and novel mutations of the COL7A1 gene in central Europe: significance for future mutation detection strategies in dystrophic epidermolysis bullosa. Br J Dermatol. 2005;152:879-86 pubmed..Reporting of three novel COL7A1 mutations in this study further emphasizes the molecular heterogeneity of DEB and provides more information for studies on genotype-phenotype correlations in different DEB subtypes. ..
- Gardella R, Castiglia D, Posteraro P, Bernardini S, Zoppi N, Paradisi M, et al. Genotype-phenotype correlation in italian patients with dystrophic epidermolysis bullosa. J Invest Dermatol. 2002;119:1456-62 pubmed..Altogether recurrent mutations account for approximately 43% of RDEB alleles in Italian patients and therefore new DEB patients should first be screened for the presence of these mutations. ..
- Gardella R, Zoppi N, Zambruno G, Barlati S, Colombi M. Different phenotypes in recessive dystrophic epidermolysis bullosa patients sharing the same mutation in compound heterozygosity with two novel mutations in the type VII collagen gene. Br J Dermatol. 2002;147:450-7 pubmed..In the other patient, the 4965C-->T splicing mutation allows the synthesis of a certain quantity of normal chains and the consequent assembly of partially functional COLVII molecules and AF, thus explaining the mild phenotype. ..
- Terracina M, Posteraro P, Schubert M, Sonego G, Atzori F, Zambruno G, et al. Compound heterozygosity for a recessive glycine substitution and a splice site mutation in the COL7A1 gene causes an unusually mild form of localized recessive dystrophic epidermolysis bullosa. J Invest Dermatol. 1998;111:744-50 pubmed
- Almaani N, Liu L, Perez A, Robson A, Mellerio J, McGrath J. Epidermolysis bullosa pruriginosa in association with lichen planopilaris. Clin Exp Dermatol. 2009;34:e825-8 pubmed publisher..Intriguingly, treatment with topical tacrolimus 0.03% led to marked improvement in the inflammation on the legs but had little effect on the scalp. ..
- Woodley D, Hou Y, Martin S, Li W, Chen M. Characterization of molecular mechanisms underlying mutations in dystrophic epidermolysis bullosa using site-directed mutagenesis. J Biol Chem. 2008;283:17838-45 pubmed publisher..We conclude that known recessive DEB C7 mutations perturb critical functions of the C7 molecule and likely contribute to the clinical phenotypes of DEB patients. ..
- Perez V, Benavides J, Delgado L, Reyes L, García Marín J, Ferreras M. Dystrophic epidermolysis bullosa in Assaf lambs. J Comp Pathol. 2011;145:226-30 pubmed publisher..Immunohistochemical analysis revealed absence of collagen VII in the basement membrane zone. The disease in these lambs appears similar to the severe recessive form of human DEB. ..
- Hayashi M, Kawaguchi M, Hozumi Y, Nakano H, Sawamura D, Suzuki T. Dystrophic epidermolysis bullosa pruriginosa of elderly onset. J Dermatol. 2011;38:173-8 pubmed publisher..Why the onset of skin fragility should have occurred so late is not known, but the case serves as a reminder that this particular mechanobullous disease can have a delayed presentation. ..
- Shi B, Feng J. A novel missense mutation in the COL7A1 gene causes epidermolysis bullosa pruriginosa. Clin Exp Dermatol. 2009;34:e975-8 pubmed publisher..This report adds new variants to the known COL7A1 mutations underlying EB pruriginosa, and provides the basis for genetic counselling and prenatal diagnosis for affected families. ..
- Bernardis C, Box R. Surgery of the hand in recessive dystrophic epidermolysis bullosa. Dermatol Clin. 2010;28:335-41, xi pubmed publisher..Meticulous skin care and the use of well-fitted splints supervised within a multidisciplinary team setting are essential. To date there is no strong evidence base on which to plan surgical treatment of the hand in DEB. ..
- Fassihi H, Lu L, Wessagowit V, Ozoemena L, Jones C, Dopping Hepenstal P, et al. Complete maternal isodisomy of chromosome 3 in a child with recessive dystrophic epidermolysis bullosa but no other phenotypic abnormalities. J Invest Dermatol. 2006;126:2039-43 pubmed..The severity of the HS-RDEB in this case was similar to other affected individuals and no additional phenotypic abnormalities were observed, suggesting an absence of maternally imprinted genes on chromosome 3. ..
- Tamai K, Hashimoto I, Hanada K, Ikeda S, Imamura S, Ogawa H. Japanese guidelines for diagnosis and treatment of junctional and dystrophic epidermolysis bullosa. Arch Dermatol Res. 2003;295 Suppl 1:S24-8 pubmed
- Christiano A, Hoffman G, Chung Honet L, Lee S, Cheng W, Uitto J, et al. Structural organization of the human type VII collagen gene (COL7A1), composed of more exons than any previously characterized gene. Genomics. 1994;21:169-79 pubmed..The COL7A1 promoter region is found to lack extensive homologies with promoter regions of other genes expressed primarily in skin. ..
- Cuadrado Corrales N, Sánchez Jimeno C, Garcia M, Escamez M, Illera N, Hernandez Martin A, et al. A prevalent mutation with founder effect in Spanish Recessive Dystrophic Epidermolysis Bullosa families. BMC Med Genet. 2010;11:139 pubmed publisher..6527insC mutation. Haplotype analysis showed that all alleles carrying the c.6527insC mutation shared the same haplotype cosegregating with this mutation (CCGCTCAAA_6527insC), thus suggesting the presence of a common ancestor. ..
- Christiano A, McGrath J, Tan K, 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 pubmed..Inspection of the locations of the glycine substitutions along the COL7A1 polypeptide suggests that the consequences of these mutations, in terms of phenotype and pattern of inheritance, are position independent. ..
- Kim J, Kim S, Yasukawa K, Shimizu H. Compound heterozygosity for premature termination codon and glycine substitution mutations in the COL7A1 gene in Korean siblings with a moderately severe phenotype of recessive dystrophic epidermolysis bullosa. J Dermatol Sci. 2003;33:180-3 pubmed
- Oh S, Lee J, Kim M, Kim S. COL7A1 mutational analysis in Korean patients with dystrophic epidermolysis bullosa. Br J Dermatol. 2007;157:1260-4 pubmed
- Wertheim Tysarowska K, Sobczynska Tomaszewska A, Kowalewski C, Skroński M, Swięćkowski G, Kutkowska Kazmierczak A, et al. The COL7A1 mutation database. Hum Mutat. 2012;33:327-31 pubmed publisher..separated values) data format download option. This compilation of COL7A1 data and nomenclature is aimed at assisting molecular and clinical geneticists to enhance the collaboration between researchers worldwide. ..
- 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 pubmed publisher..Thus intradermal administration of allogeneic MSC associates with type VII collagen replenishment at the dermal-epidermal junction, prevents blistering and improves wound healing in unconditioned patients with RDEB. ..
- Escámez M, Garcia M, Cuadrado Corrales N, Llames S, Charlesworth A, De Luca N, et al. The first COL7A1 mutation survey in a large Spanish dystrophic epidermolysis bullosa cohort: c.6527insC disclosed as an unusually recurrent mutation. Br J Dermatol. 2010;163:155-61 pubmed publisher..They also provide geneticists a molecular clue for a priority mutation screening strategy. ..
- Masunaga T, Shimizu H, Takizawa Y, Uitto J, Nishikawa T. Combination of novel premature termination codon and glycine substitution mutations in COL7A1 leads to moderately severe recessive dystrophic epidermolysis bullosa. J Invest Dermatol. 2000;114:204-5 pubmed
- van den Akker P, Jonkman M, Rengaw T, Bruckner Tuderman L, Has C, Bauer J, et al. The international dystrophic epidermolysis bullosa patient registry: an online database of dystrophic epidermolysis bullosa patients and their COL7A1 mutations. Hum Mutat. 2011;32:1100-7 pubmed publisher..Altogether, this registry will greatly benefit the DEB patients. ..
- Ishiko A, Masunaga T, Ota T, Nishikawa T. Does the position of the premature termination codon in COL7A1 correlate with the clinical severity in recessive dystrophic epidermolysis bullosa?. Exp Dermatol. 2004;13:229-33 pubmed..Therefore, genotype-phenotype relationships in RDEB cannot be explained purely by the position of PTC. ..
- Masse M, Cserhalmi Friedman P, Falanga V, Celebi J, Martinez Mir A, Christiano A. Identification of novel type VII collagen gene mutations resulting in severe recessive dystrophic epidermolysis bullosa. Clin Exp Dermatol. 2005;30:289-93 pubmed..To our knowledge, these two mutations have not been previously reported. These findings extend the body of evidence for compound heterozygous mutations leading to HS-RDEB and provide the basis for prenatal diagnosis in this family. ..
- Culpepper T. Anesthetic implications in epidermolysis bullosa dystrophica. AANA J. 2001;69:114-8 pubmed..Successful anesthetic management of a patient with epidermolysis bullosa is possible if precautions with anesthetic instrumentation are observed. ..
- Tey H, Lee A, Almaani N, McGrath J, Mills K, Yosipovitch G. Epidermolysis bullosa pruriginosa masquerading as psychogenic pruritus. Arch Dermatol. 2011;147:956-60 pubmed publisher..Patients with this inherited skin disorder can be easily misdiagnosed as having psychogenic pruritus, and this article aims to make physicians aware of this diagnostic pitfall. ..
- Lehman T, Morgan T, Lehman N, Vogel H, McGuire J. Recessive dystrophic epidermolysis bullosa associated with mesangioproliferative glomerulonephritis and multifocal necrotizing leucoencephalopathy of the pons. Br J Dermatol. 2004;151:1266-9 pubmed..Although mesangioproliferative glomerulonephritis has previously been described in association with RDEB, to our knowledge this is the first report of MNL in a patient with RDEB. ..
- Wagner J, Ishida Yamamoto A, McGrath J, Hordinsky M, Keene D, Woodley D, et al. Bone marrow transplantation for recessive dystrophic epidermolysis bullosa. N Engl J Med. 2010;363:629-39 pubmed publisher..Further studies are needed to assess the long-term risks and benefits of such therapy in patients with this disorder. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00478244.) ..
- Medeiros G, Riet Correa F, Barros S, Soares M, Dantas A, Galiza G, et al. Dystrophic epidermolysis bullosa in goats. J Comp Pathol. 2013;148:354-60 pubmed publisher..It is suggested that the disease is similar to human severe generalized recessive DEB...
- Pasmooij A, Garcia M, Escamez M, Nijenhuis A, Azon A, Cuadrado Corrales N, et al. Revertant mosaicism due to a second-site mutation in COL7A1 in a patient with recessive dystrophic epidermolysis bullosa. J Invest Dermatol. 2010;130:2407-11 pubmed publisher..Furthermore, the revertant keratinocytes might offer the possibility to explore cell-based therapeutic strategies, by culturing in vitro and subsequently grafting as part of bioengineered dermo-epidermal substitutes on affected skin. ..
- Yonei N, Ohtani T, Furukawa F. Recessive dystrophic epidermolysis bullosa: case of non-Hallopeau-Siemens variant with premature termination codons in both alleles. J Dermatol. 2006;33:802-5 pubmed
- Jiang W, Sun Y, Li S, Chen X, Bu D, Zhu X. Two novel heterozygous mutations in COL7A1 in a Chinese patient with recessive dystrophic epidermolysis bullosa of Hallopeau-Siemens type. Br J Dermatol. 2005;152:1357-9 pubmed
- Horn H, Tidman M. The clinical spectrum of dystrophic epidermolysis bullosa. Br J Dermatol. 2002;146:267-74 pubmed..Scarring, gastrointestinal involvement, albopapuloid lesions and a pruriginosa-like pattern each occur in both DDEB and RDEB. With increasing age, SCC is a major cause of morbidity and mortality. ..
- Shimizu H, Hammami Hauasli N, Hatta N, Nishikawa T, Bruckner Tuderman L. Compound heterozygosity for silent and dominant glycine substitution mutations in COL7A1 leads to a marked transient intracytoplasmic retention of procollagen VII and a moderately severe dystrophic epidermolysis bullosa phenotype. J Invest Dermatol. 1999;113:419-21 pubmed
- Oliveira T, Sakai V, Candido L, Silva S, Machado M. Clinical management for epidermolysis bullosa dystrophica. J Appl Oral Sci. 2008;16:81-5 pubmed..The psychological intervention required during the dental treatment of these patients is also presented. ..
- Leverkus M, Ambach A, Hoefeld Fegeler M, Kohlhase J, Schmidt E, Schumann H, et al. Late-onset inversa recessive dystrophic epidermolysis bullosa caused by glycine substitutions in collagen type VII. Br J Dermatol. 2011;164:1104-6 pubmed publisher..3 We report a German patient with an unusually mild RDEB-I harbouring compound heterozygous mutations in COL7A1. ..
- Covaciu C, Grosso F, Pisaneschi E, Zambruno G, Gregersen P, Sommerlund M, et al. A founder synonymous COL7A1 mutation in three Danish families with dominant dystrophic epidermolysis bullosa pruriginosa identifies exonic regulatory sequences required for exon 87 splicing. Br J Dermatol. 2011;165:678-82 pubmed publisher..These findings substantiate for the first time the involvement of an ESE mutation in the pathogenesis of DEB and have implications for genetic counselling of Danish families with DDEB. ..
- Christiano A, McGrath J, Uitto J. Influence of the second COL7A1 mutation in determining the phenotypic severity of recessive dystrophic epidermolysis bullosa. J Invest Dermatol. 1996;106:766-70 pubmed..These results define M-RDEB as a distinct clinical entity at the molecular level. ..
- Christiano A, Greenspan D, Hoffman G, Zhang X, Tamai Y, Lin A, et al. A missense mutation in type VII collagen in two affected siblings with recessive dystrophic epidermolysis bullosa. Nat Genet. 1993;4:62-6 pubmed..The mutation resides in a highly conserved region of the C-terminus of type VII collagen, strongly suggesting that it is the cause of the disease in this family. ..
- Ryoo Y, Kim B, Lee K. Characterization of mutations of the type VII collagen gene (COL7A1) in recessive dystrophic epidermolysis bullosa mitis (M-RDEB) from three Korean patients. J Dermatol Sci. 2001;26:125-32 pubmed..We hope that these data contribute to the expanding database on COL7A1 mutations in dystrophic epidermolysis bullosa, and further illustrate the extensive diversity of mutational events that led to the RDEB phenotype. ..