title: Heterozygosity for a Novel Missense Mutation in the ITGB4 Gene Associated With Autosomal Dominant Epidermolysis Bullosa.
abstract: OBJECTIVE
  Epidermolysis bullosa (EB) is a group of mechanobullous genodermatoses characterized by the fragility of skin and mucous membranes. Mutations in the ITGA6 and ITGB4 genes, encoding the hemidesmosomal protein α6β4-integrin, have been involved in the pathogenesis of EB. To date, the inheritance of these particular genes is known to be exclusively autosomal recessive. Herein, we report a novel heterozygous missense mutation in the ITGB4 gene exerting a dominant negative effect that cosegregates with the EB phenotype in an extended family.
  
  
  METHODS
  The clinical phenotype of affected individuals is primarily characterized by nail dystrophy and late onset of mild skin fragility and acral blistering. Some patients developed granulation tissue in the larynx, urethra, lacrimal duct, and external auditory canal. Sequencing the complete set of genes associated with EB revealed a heterozygous missense mutation in exon 5 of ITGB4: c.433G>T, p.Asp145Tyr. The mutation was found in the affected relatives and was not present in unaffected relatives and control DNA samples.
  
  
  CONCLUSIONS
  This study highlights, for the first time to our knowledge, the possibility of a dominant mode of inheritance for a missense ITGB4 mutation in EB, thus expanding the mutational database and genotype-phenotype correlation for this rare disease.
authors.affiliation: Department of Dermatology, Center for Blistering Diseases, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Iana
authors.initials: I
authors.lastname: Turcan
authors.affiliation: Department of Dermatology, Center for Blistering Diseases, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Anna M G
authors.initials: AM
authors.lastname: Pasmooij
authors.affiliation: Department of Dermatology, Center for Blistering Diseases, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands, 2Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Neth.
authors.forename: Peter C
authors.initials: PC
authors.lastname: van den Akker
authors.affiliation: Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Henny
authors.initials: H
authors.lastname: Lemmink
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Gyorgy B
authors.initials: GB
authors.lastname: Halmos
authors.affiliation: Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Sinke
authors.affiliation: Department of Dermatology, Center for Blistering Diseases, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Marcel F
authors.initials: MF
authors.lastname: Jonkman
mesh_terms: D004820:Epidermolysis Bullosa / Q000235:genetics* / Q000473:pathology; D005091:Exons / Q000235:genetics; D005190:Family; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D039663:Integrin beta4 / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D009260:Nail Diseases / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D010641:Phenotype
chemical_list: C059834:ITGB4 protein, human; D039663:Integrin beta4