Bullous pemphigoid antigens (BPAGs): identification of RFLPs in human BPAG1 and BPAG2, and exclusion as candidate genes in a large kindred with dominant epidermolysis bullosa simplex.
Bullous pemphigoid antigens (BPAGs) are defined as autoantigens in a blistering skin disease, bullous pemphigoid. Two of the BPAGs, a 230-kD (BPAG1) and a 180-kD (BPAG2) protein, have been localized to hemidesmosomes, attachment structures at the basal keratinocyte-basement membrane interphase. We have recently cloned cDNAs corresponding to human BPAG1 and BPAG2, and mapped the corresponding genes to human chromosomes 6p and 10q, respectively. These cDNAs have now been used in a search for RFLPs in the corresponding genes. Southern hybridizations of genomic DNA from normal unrelated individuals with a BPAG1 cDNA detected an informative MspI RFLP, and similar hybridizations with a BPAG2 cDNA revealed an informative TaqI RFLP. These RFLPs were applied to a large kindred with epidermolysis bullosa simplex (EBS), generalized (Koebner) type, consisting of 14 affected and 12 unaffected individuals in three generations. Linkage analysis excluded the EBS locus in this pedigree approximately 9 cM and approximately 5 cM on either side of the BPAG1 and BPAG2 loci, respectively, when a lod score of -2.0 was taken as the limit of exclusion. This study demonstrates that mutations in the BPAG1 or BPAG2 genes are not the primary genetic defect in this family with EBS.
Ryynänen
M
M
Department of Dermatology, Jefferson Medical College, Philadelphia, Pennsylvania.
Knowlton
R G
RG
Kero
M
M
Sawamura
D
D
Li
K H
KH
Giudice
G J
GJ
Diaz
L A
LA
Uitto
J
J
D001324:Autoantigens / Q000235:genetics*; D015139:Blotting, Southern; D002352:Carrier Proteins; D003094:Collagen; D003598:Cytoskeletal Proteins; D000071821:Dystonin; D016110:Epidermolysis Bullosa Simplex / Q000235:genetics* / Q000276:immunology; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D008126:Lod Score; D008297:Male; D009154:Mutation; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D010375:Pedigree; D010391:Pemphigoid, Bullous / Q000235:genetics* / Q000276:immunology; D012150:Polymorphism, Restriction Fragment Length; D000097805:Collagen Type XVII
D001324:Autoantigens; D002352:Carrier Proteins; D003094:Collagen; D003598:Cytoskeletal Proteins; D000071821:Dystonin; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D000097805:Collagen Type XVII; C486268:DST protein, human