292 Heterozygous pathogenic variants affecting the the highly conserved VWFA domain of integrin-β4 cause isolated nail dystrophy

Pathogenic variants in ITGB4 cause various forms of autosomal recessive epidermolysis bullosa (EB). encodes integrin-β4, which plays a critical role the maintenance skin basement membrane integrity. Here, we aimed to delineate genetic basis dominant isolated nail dystrophy 2 families. We studied total five affected individuals with and no other cutaneous or extra-cutaneous findings. Whole exome sequencing revealed different heterozygous missense variant gene each Both mutations co-segregated disease phenotype families, were classified as pathogenic by prediction tools are ultra-rare. Of interest, protein modeling that two well previously identified dystrophy-causing mutation, clustered within highly conserved VWFA domain integrin-β4 predicted structural changes mis-folding. In conclusion, affecting dystrophy.