Compound heterozygosity for a point mutation and a deletion located at splice acceptor sites in the LAMB3 gene leads to generalized atrophic benign epidermolysis bullosa

An autosomal recessive disorder, generalized atrophic benign epidermolysis bullosa, is a rare form of nonlethal type junctional epidermolysis bullosa. It is associated not only with skin fragility but also with other unique c linical features including widespread atrophic skin changes, alopecia, redu ced axillary and pubic hair, dysplastic teeth, and dystrophic nails. The ma jority of generalized atrophic benign epidermolysis bullosa cases are cause d by mutations in the COL17A1 gene coding for type XVII collagen (or the 18 0 kDa bullous pemphigoid antigen). Another candidate gene for mutations in some forms of generalized atrophic benign epidermolysis bullosa is LAMB3 en coding the beta 3 chain of laminin 5. This report documents compound hetero zygosity for novel mutations in LAMB3 of a Japanese patient showing typical clinical features of generalized atrophic benign epidermolysis bullosa. On e is an A-to-G transversion at the splice acceptor site of intron 14, which is designated as a 1977-2A --> G mutation; the other is a deletion of 94 b p located at the junction of intron 18 and exon 19, which is a 2702-29del94 mutation. Reverse transcriptase polymerase chain reaction analysis suggest ed skipping of exon 19 in LAMB3 mRNA produced from the allele with 2702-29d el94 and impaired stability of the aberrant mRNA transcribed from the secon d allele with the 1977-2A --> G mutation.