TY - JOUR
T1 - Pretibial dystrophic epidermolysis bullosa
T2 - A recessively inherited COL7A1 splice site mutation affecting procollagen VII processing
AU - Betts, Christine M.
AU - Posteraro, P.
AU - Costa, A. M.
AU - Varotti, C.
AU - Schubert, M.
AU - Bruckner-Tuderman, L.
AU - Castiglia, D.
PY - 1999
Y1 - 1999
N2 - Pretibial epidermolysis bullosa (PEB) is a rare form of localized epidermolysis bullosa dystrophica (EBD), a heterogeneous group of inherited, blistering diseases characterized by scarring, loss of dermal-epidermal adhesion and altered anchoring fibrils (AF). Mutations in the type VII collagen gene (COL7A1) underlie EBD and in a dominant PEB family a glycine substitution mutation has been identified. We report a 33-year-old man affected by PEB showing abnormal AF and reduced immunostaining for type VII collagen. Mutation search in the COL7A1 gene revealed a 14 bp deletion in the 115 exon-intron boundary (33563del14), which resulted in the in-frame skipping of exon 115 with elimination of 29 amino acids from the pro-α1(VII) polypeptide chain. As a consequence, procollagen VII failed to be processed to mature collagen VII and accumulated at the dermal-epidermal junction, as revealed by immunofluorescence staining using a NC-2 domain-specific antibody. The proband's father was a clinically unaffected heterozygous carrier of mutation 33563del14, whereas the maternal pathogenetic mutation has still not been identified. This represents the first report of a recessive deletion mutation in PEB and extends the range of EBD phenotypes associated with mutation 33563del14.
AB - Pretibial epidermolysis bullosa (PEB) is a rare form of localized epidermolysis bullosa dystrophica (EBD), a heterogeneous group of inherited, blistering diseases characterized by scarring, loss of dermal-epidermal adhesion and altered anchoring fibrils (AF). Mutations in the type VII collagen gene (COL7A1) underlie EBD and in a dominant PEB family a glycine substitution mutation has been identified. We report a 33-year-old man affected by PEB showing abnormal AF and reduced immunostaining for type VII collagen. Mutation search in the COL7A1 gene revealed a 14 bp deletion in the 115 exon-intron boundary (33563del14), which resulted in the in-frame skipping of exon 115 with elimination of 29 amino acids from the pro-α1(VII) polypeptide chain. As a consequence, procollagen VII failed to be processed to mature collagen VII and accumulated at the dermal-epidermal junction, as revealed by immunofluorescence staining using a NC-2 domain-specific antibody. The proband's father was a clinically unaffected heterozygous carrier of mutation 33563del14, whereas the maternal pathogenetic mutation has still not been identified. This represents the first report of a recessive deletion mutation in PEB and extends the range of EBD phenotypes associated with mutation 33563del14.
KW - Anchoring fibrils
KW - COL7A1 mutation
KW - Epidermolysis bullosa dystrophica
KW - Pretibial epidermolysis bullosa
UR - http://www.scopus.com/inward/record.url?scp=0032713149&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032713149&partnerID=8YFLogxK
U2 - 10.1046/j.1365-2133.1999.03155.x
DO - 10.1046/j.1365-2133.1999.03155.x
M3 - Article
C2 - 10583163
AN - SCOPUS:0032713149
VL - 141
SP - 833
EP - 839
JO - British Journal of Dermatology
JF - British Journal of Dermatology
SN - 0007-0963
IS - 5
ER -