Homozygous ITGA3 Missense Mutation in Adults in a Family with Syndromic Epidermolysis Bullosa

Epidermolysis bullosa (EB), the prototype of skin fragility disorders, manifests with blistering and erosions of the skin and mucous membranes. In some cases, the clinical manifestations are limited to the skin, i.e., being non-syndromic, while in others the skin manifestations are associated with extracutaneous findings, thus being syndromic. The classic forms of EB are associated with 16 distinct genes expressed in the cutaneous basement membrane zone. One such gene is ITGA3 encoding alpha3 integrin subunit, which combines with beta1 subunit to form alpha3beta1 integrin. Mutations in the ITGA3 gene have been reported in 10 cases with EB, and the characteristic feature in the majority of these patients is severe respiratory and renal involvement that can lead to the early postnatal demise of the affected individuals. This subtype of EB, known as EB-RR, has also been dubbed as ILNEB (interstitial lung disease, nephrotic syndrome, and epidermolysis bullosa) (OMIM 614748). The pathogenic sequence variants in these cases are characteristically loss-of-function mutations, and EB due to ITGA3 mutations has been considered to be a severe lethal condition. In this study, we report two adult males, 45 and 30 years of age, with EB associated with a homozygous missense mutation in ITGA3.