Heterozygosity for a Novel Missense Mutation in the ITGB4 Gene Associated With Autosomal Dominant Epidermolysis Bullosa.

IMPORTANCE: 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.

OBSERVATIONS: 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 AND RELEVANCE: 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.