COLLAGEN-VII IN SEVERE RECESSIVE DYSTROPHIC EPIDERMOLYSIS-BULLOSA - EXPRESSION OF MESSENGER-RNA BUT LACK OF INTACT PROTEIN PRODUCT IN SKIN AND CUTANEOUS CELLS IN-VITRO

The collagen VII gene, COL7A1, is the candidate gene for both the rece ssive and dominant forms of dystrophic epidermolysis bullosa (EBD). Co llagen VII is a structural protein of the anchoring fibrils, which are rudimentary or altered in several subtypes of EBD. In severe recessiv e mutilating EBD, anchoring fibrils and collagen VII are not detectabl e in skin of most patients. To elucidate the underlying pathogenetic m echanisms, we analyzed collagen VII expression in cutaneous cells of s ix patients with this severe EBD subtype. Neither keratinocytes nor fi broblasts synthesized detectable amounts of collagen VII protein; howe ver, Northern blot analysis revealed small amounts of normal-size coll agen VII mRNA in both EBD and control fibroblasts. When the mRNA was a mplified using reverse transcription-polymerase chain reaction, correc t amplimers were present in all specimens. The results demonstrate tha t transcription of the COL7A1 gene occurs in these patients with sever e mutilating EBD and suggest that post-transcriptional or posttranslat ional events lead to absence of collagen VII protein from skin.