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Integrin β4 (ITGB4) encodes the cytoplasmic subunit of the α6β4 hemidesmosomal integrin essential for keratinocyte–matrix adhesion. A single autosomal recessive case of epidermolysis bullosa simplex (EBS) has been described in a 49-year-old female with lifelong mild blistering of hands and feet, nail dystrophy, and enamel hypoplasia due to compound heterozygous ITGB4 mutations. The patient harbored a splice-site variant c.5329+2T>C and a frameshift deletion c.4574_4575del (p.Ala1525ProfsTer?) leading to in-frame loss of the third fibronectin type III repeat, resulting in absent β4 epitope binding and intraepidermal cleavage on electron microscopy (PMID:12485428). Functional studies including immunofluorescence and immunoblot demonstrated loss of full-length β4 and disrupted hemidesmosome assembly, supporting a loss-of-function mechanism. No additional unrelated cases or formal segregation data have been reported, limiting the genetic evidence. Clinically, this case expands the ITGB4-associated spectrum to a mild EBS phenotype without pyloric atresia and supports inclusion of ITGB4 in diagnostic gene panels for vesiculobullous disorders.
Key Take-home: ITGB4 pathogenic variants can underlie a mild, autosomal recessive EBS subtype and should be considered in genetically undiagnosed blistering diseases.
Gene–Disease AssociationLimitedSingle proband report, no segregation Genetic EvidenceLimitedOne compound heterozygous case, no additional unrelated affected Functional EvidenceModerateImmunofluorescence and immunoblot show loss of β4 and hemidesmosome disruption |