The international dystrophic epidermolysis bullosa patient registry: An online database of dystrophic epidermolysis bullosa patients and their COL7A1 mutations

Dystrophic epidermolysis bullosa (DEB) is a heritable blistering disorder that can be inherited autosomal dominantly (DDEB) or recessively (RDEB) and covers a group of several distinctive phenotypes. A large number of unique COL7A1 mutations have been shown to underlie DEB. Although general genotype–phenotype correlation rules have emerged, many exceptions to these rules exist, compromising disease diagnosing and genetic counseling. We therefore constructed the International DEB Patient Registry (http://www.deb‐central.org), aimed at worldwide collection and sharing of phenotypic and genotypic information on DEB. As of May 2011, this MOLGENIS‐based registry contains detailed information on 508 published and 71 unpublished patients and their 388 unique COL7A1 mutations, and includes all combinations of mutations. The current registry RDEB versus DDEB ratio of 4:1, if compared to prevalence figures, suggests underreporting of DDEB in the literature. Thirty‐eight percent of mutations stored introduce a premature termination codon (PTC) and 43% an amino acid change. Submission wizards allow users to quickly and easily share novel information. This registry will be of great help in disease diagnosing and genetic counseling and will lead to novel insights, especially in the rare phenotypes of which there is often lack of understanding. Altogether, this registry will greatly benefit the DEB patients. Hum Mutat 32:1100–1107, 2011. ©2011 Wiley‐Liss, Inc.

[1]  J. Uitto,et al.  Recurrent mutations in the type VII collagen gene (COL7A1) in patients with recessive dystrophic epidermolysis bullosa. , 1997, The Journal of investigative dermatology.

[2]  H. Shimizu,et al.  Genetic studies of 20 Japanese families of dystrophic epidermolysis bullosa , 2005, Journal of Human Genetics.

[3]  Eady,et al.  A recurrent glycine substitution mutation, G2043R, in the type VII collagen gene (COL7A1) in dominant dystrophic epidermolysis bullosa , 1998, The British journal of dermatology.

[4]  S. Llames,et al.  The first COL7A1 mutation survey in a large Spanish dystrophic epidermolysis bullosa cohort: c.6527insC disclosed as an unusually recurrent mutation , 2010, The British journal of dermatology.

[5]  P. Krajči,et al.  Modulation of disease severity of dystrophic epidermolysis bullosa by a splice site mutation in combination with a missense mutation in the COL7A1 gene. , 1997, Human molecular genetics.

[6]  L. Bruckner-Tuderman,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 , 2005, The British journal of dermatology.

[7]  C. Has,et al.  Forty‐two novel COL7A1 mutations and the role of a frequent single nucleotide polymorphism in the MMP1 promoter in modulation of disease severity in a large European dystrophic epidermolysis bullosa cohort , 2009, The British journal of dermatology.

[8]  F. Melton.  Epidermolysis bullosa. , 1955, A.M.A. archives of dermatology.

[9]  J. McGrath,et al.  Genotype-phenotype correlation in italian patients with dystrophic epidermolysis bullosa. , 2002, The Journal of investigative dermatology.

[10]  J. Uitto,et al.  Influence of the second COL7A1 mutation in determining the phenotypic severity of recessive dystrophic epidermolysis bullosa. , 1996, The Journal of investigative dermatology.

[11]  J. Uitto,et al.  Structural organization of the human type VII collagen gene (COL7A1), composed of more exons than any previously characterized gene. , 1994, Genomics.

[12]  G. Priestley,et al.  The prevalence of epidermolysis bullosa in Scotland , 1997, The British journal of dermatology.

[13]  C. Has,et al.  Expanding the COL7A1 mutation database: novel and recurrent mutations and unusual genotype-phenotype constellations in 41 patients with dystrophic epidermolysis bullosa. , 2006, The Journal of investigative dermatology.

[14]  C. Has,et al.  Dystrophic epidermolysis bullosa pruriginosa is not associated with frequent FLG gene mutations , 2008, The British journal of dermatology.

[15]  J. McGrath,et al.  New glycine substitution mutations in type VII collagen underlying epidermolysis bullosa pruriginosa but the phenotype is not explained by a common polymorphism in the matrix metalloproteinase-1 gene promoter. , 2009, Acta dermato-venereologica.

[16]  K. Wiss.  Epidermolysis bullosa: Clinical, epidemiologic, and laboratory advances and the findings of the National Epidermolysis Bullosa Registry , 2001 .

[17]  J. Uitto,et al.  Epidermolysis bullosa. II. Type VII collagen mutations and phenotype–genotype correlations in the dystrophic subtypes , 2006, Journal of Medical Genetics.

[18]  E. Bauer,et al.  The classification of inherited epidermolysis bullosa (EB): Report of the Third International Consensus Meeting on Diagnosis and Classification of EB. , 2008, Journal of the American Academy of Dermatology.

[19]  Morris A. Swertz,et al.  Beyond standardization: dynamic software infrastructures for systems biology , 2007, Nature Reviews Genetics.

[20]  J. McGrath,et al.  The molecular basis of dystrophic epidermolysis bullosa in Mexico , 2000, International journal of dermatology.

[21]  Damian Smedley,et al.  XGAP: a uniform and extensible data model and software platform for genotype and phenotype experiments , 2010, Genome Biology.

[22]  R. Hofstra,et al.  Long-term follow-up of patients with recessive dystrophic epidermolysis bullosa in the Netherlands: expansion of the mutation database and unusual phenotype-genotype correlations. , 2009, Journal of dermatological science.

[23]  H. Shimizu,et al.  Differences in recurrent COL7A1 mutations in dystrophic epidermolysis bullosa: ethnic-specific and worldwide recurrent mutations , 2004, Archives of Dermatological Research.

[24]  E. Bauer,et al.  Revised clinical and laboratory criteria for subtypes of inherited epidermolysis bullosa. A consensus report by the Subcommittee on Diagnosis and Classification of the National Epidermolysis Bullosa Registry. , 1991, Journal of the American Academy of Dermatology.

[25]  L. Bruckner-Tuderman,et al.  Hereditary skin diseases of anchoring fibrils. , 1999, Journal of dermatological science.

[26]  L. Bruckner-Tuderman,et al.  Immunohistochemical and mutation analyses demonstrate that procollagen VII is processed to collagen VII through removal of the NC-2 domain , 1995, The Journal of cell biology.

[27]  J. Q. Rosso,et al.  Epidermolysis bullosa and the risk of life-threatening cancers: The National EB Registry experience, 1986-2006 , 2010 .

[28]  M. Indelman,et al.  Molecular epidemiology of hereditary epidermolysis bullosa in a Middle Eastern population. , 2006, The Journal of investigative dermatology.

[29]  Morris A. Swertz,et al.  The MOLGENIS toolkit: rapid prototyping of biosoftware at the push of a button , 2010, BMC Bioinformatics.

[30]  Characterization of 18 new mutations in COL7A1 in recessive dystrophic epidermolysis bullosa provides evidence for distinct molecular mechanisms underlying defective anchoring fibril formation. , 1997, American journal of human genetics.

[31]  R. Burgeson,et al.  Premature termination codon mutations in the type VII collagen gene in recessive dystrophic epidermolysis bullosa result in nonsense-mediated mRNA decay and absence of functional protein. , 1997, The Journal of investigative dermatology.

[32]  D. Murrell,et al.  Review of collagen VII sequence variants found in Australasian patients with dystrophic epidermolysis bullosa reveals nine novel COL7A1 variants. , 2007, Journal of dermatological science.

[33]  C. Bodemer,et al.  A frequent functional SNP in the MMP1 promoter is associated with higher disease severity in recessive dystrophic epidermolysis bullosa , 2008, Human mutation.

[34]  J. McGrath,et al.  Identical glycine substitution mutations in type VII collagen may underlie both dominant and recessive forms of dystrophic epidermolysis bullosa. , 2011, Acta dermato-venereologica.

[35]  R. Hofstra,et al.  The inversa type of recessive dystrophic epidermolysis bullosa is caused by specific arginine and glycine substitutions in type VII collagen , 2010, Journal of Medical Genetics.

[36]  J. Uitto,et al.  Cloning of human type VII collagen. Complete primary sequence of the alpha 1(VII) chain and identification of intragenic polymorphisms. , 1994, The Journal of biological chemistry.

[37]  E. Bauer,et al.  Revised classification system for inherited epidermolysis bullosa: Report of the Second International Consensus Meeting on diagnosis and classification of epidermolysis bullosa. , 2000, Journal of the American Academy of Dermatology.

[38]  C. Chiaverini,et al.  Inversa dystrophic epidermolysis bullosa is caused by missense mutations at specific positions of the collagenic domain of collagen type VII. , 2010, The Journal of investigative dermatology.

[39]  J. Uitto,et al.  Clinicopathological correlations of compound heterozygous COL7A1 mutations in recessive dystrophic epidermolysis bullosa. , 1996, The Journal of investigative dermatology.

[40]  S. Antonarakis,et al.  Mutation nomenclature extensions and suggestions to describe complex mutations: A discussion , 2000 .

[41]  L. Fajkusová,et al.  Analysis of the COL7A1 gene in Czech patients with dystrophic epidermolysis bullosa reveals novel and recurrent mutations. , 2010, Journal of dermatological science.

[42]  H. Shimizu,et al.  Recurrent COL7A1 mutations in Japanese patients with dystrophic epidermolysis bullosa: positional effects of premature termination codon mutations on clinical severity. Japanese Collaborative Study Group on Epidermolysis Bullosa. , 1999, The Journal of investigative dermatology.

[43]  Mohammedi,et al.  A recurrent COL7A1 mutation, R2814X, in British patients with recessive dystrophic epidermolysis bullosa , 1999, Clinical and experimental dermatology.