{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T05:40:21Z","timestamp":1759729221476,"version":"build-2065373602"},"reference-count":30,"publisher":"BMJ","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1994,10]]},"abstract":"<jats:p>To strengthen the evidence for genetic linkage to COL7A1, we have studied 26 generalised recessive dystrophic epidermolysis bullosa (EB) families of British, Italian, Irish, and South African origin. We chose two linkage markers, a COL7A1 PvuII intragenic polymorphism and a highly informative anonymous microsatellite marker, D3S1100, which maps close to the COL7A1 locus at 3p21.1-3. Diagnosis was established by family history, clinical examination, immunofluorescence, and ultrastructural studies. The PvuII marker was informative in 16 families with a maximum lod score (Zmax) of 3.51 at recombination fraction (theta) = 0. The D3S1100 microsatellite was informative in 24 out of 25 families with Zmax = 6.8 at theta = 0.05 (Z = 4.94 at theta = 0) and no obligatory recombination events. These data strongly suggest that COL7A1 mutations cause EB in these families and, combined with previous studies, indicate locus homogeneity. The importance of anchoring fibrils for dermal-epidermal adhesion is further underlined. D3S1100 may later prove useful in prenatal diagnosis of this disease, if used in combination with other markers.<\/jats:p>","DOI":"10.1136\/jmg.31.10.745","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T15:23:16Z","timestamp":1226330596000},"page":"745-748","source":"Crossref","is-referenced-by-count":24,"title":["Genetic linkage to the type VII collagen gene (COL7A1) in 26 families with generalised recessive dystrophic epidermolysis bullosa and anchoring fibril abnormalities."],"prefix":"10.1136","volume":"31","author":[{"given":"M G","family":"Dunnill","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A J","family":"Richards","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G","family":"Milana","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F","family":"Mollica","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D","family":"Atherton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I","family":"Winship","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Farrall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L","family":"al-Imara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R A","family":"Eady","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F M","family":"Pope","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1994,10,1]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Classification of epidermolysis bullosa","volume-title":"bullosa. A comprehensive review of classification, management and laboratory studies","author":"Eady, R.A.J.","year":"1990","unstructured":"Eady RAJ. Classification of epidermolysis bullosa. In: Priestley GC, Tidman MJ, Weiss JB, Eady RAJ, eds. Epidermolysis bullosa. A comprehensive review of classification, management and laboratory studies. Crowthome, Berkshire: DEBRA, 1990:1-9."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/0190-9622(91)70021-S","article-title":"Revised clinical and laboratory criteria for subtypes of inherited epidermolysis bullosa","volume":"24","author":"Fine, J.D.; Bauer, A.; Briggaman, R.A.","year":"1991","unstructured":"Fine JD, Bauer A, Briggaman RA, et al. Revised clinical and laboratory criteria for subtypes of inherited epidermolysis bullosa. _Am Acad Dermatol 1991;24:119-35.","journal-title":"_Am Acad Dermatol"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1083\/jcb.103.4.1577","article-title":"Type VII collagen is a major structural component of anchoring fibrils","volume":"103","author":"Sakai, L.Y.; Keene, D.R.; Morris, M.P.; Burgeson, R.E.","year":"1986","unstructured":"Sakai LY, Keene DR, Morris MP, Burgeson RE. Type VII collagen is a major structural component of anchoring fibrils. Cell Biol 1986;103:1577-86.","journal-title":"Cell Biol"},{"issue":"203-1","key":"ref_4","first-page":"1","article-title":"Epidermolysis bullosa dystrophica-recessive: a possible role of anchoring fibrils in the pathogenesis","volume":"65","author":"Briggaman, R.A.; Wheeler, C.E.","year":"1975","unstructured":"Briggaman RA, Wheeler CE. Epidermolysis bullosa dystrophica-recessive: a possible role of anchoring fibrils in the pathogenesis. Invest Dermatol 1975;65:203-1 1.","journal-title":"Invest Dermatol"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1111\/1523-1747.ep12265460","article-title":"Evaluation of anchoring fibrils and other components of the dermal-epidermal junction in dystrophic epidermolysis bullosa by a quantitive ultrastructural technique","volume":"84","author":"Tidman, M.J.; Eady, R.A.J.","year":"1985","unstructured":"Tidman MJ, Eady RAJ. Evaluation of anchoring fibrils and other components of the dermal-epidermal junction in dystrophic epidermolysis bullosa by a quantitive ultrastructural technique. Invest Dernatol 1985;84:374-7.","journal-title":"Invest Dernatol"},{"key":"ref_6","first-page":"125","article-title":"Identification of an epidermal basement membrane defect in recessive dystrophic epidermolysis bullosa by LH7: 2 monoclonal antibody: use in diagnosis","volume":"115","author":"Heagerty, A.H.M.; Kennedy, A.R.; Leigh, I.M.; Purkis, P.; Eady, R.A.J.","year":"1986","unstructured":"Heagerty AHM, Kennedy AR, Leigh IM, Purkis P, Eady RAJ. Identification of an epidermal basement membrane defect in recessive dystrophic epidermolysis bullosa by LH7:2 monoclonal antibody: use in diagnosis. BrJ7Dermatol 1986;115:125-31."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1159\/000248673","article-title":"Lack of type VII collagen in unaffected skin of patients with severe recessive dystrophic epidermolysis bullosa","volume":"176","author":"Bruckner-Tuderman, L.; Ruegger, S.; Odermatt, B.; Mitsuhashi, Y.; Schnyder, U.N.","year":"1988","unstructured":"Bruckner-Tuderman L, Ruegger S, Odermatt B, Mitsuhashi Y, Schnyder UN. Lack of type VII collagen in unaffected skin of patients with severe recessive dystrophic epidermolysis bullosa. Dermatologica 1988;176:57-64.","journal-title":"Dermatologica"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1111\/1523-1747.ep12560795","article-title":"Type VII collagen is a normal component of epidermal basement membrane, which shows altered expression in recessive dystrophic epidermolysis bullosa","volume":"90","author":"Leigh, I.M.; Eady, R.A.J.; Heagerty, A.H.M.; Purkis, P.E.; Whitehead, P.A.; Burgeson, E.","year":"1988","unstructured":"Leigh IM, Eady RAJ, Heagerty AHM, Purkis PE, Whitehead PA, Burgeson E. Type VII collagen is a normal component of epidermal basement membrane, which shows altered expression in recessive dystrophic epidermolysis bullosa. J Invest Dermatol 1988;90:639-42.","journal-title":"J Invest Dermatol"},{"key":"ref_9","first-page":"797","article-title":"Human type VII collagen: genetic linkage of the gene (COL7A1) on chromosome 3 to dominant dystrophic epidermolysis bullosa","volume":"49","author":"Ryynanen, M.; Knowlton, R.G.; Parente, M.G.; Chung, L.C.; Chu, M.L.; Uitto, J.","year":"1991","unstructured":"Ryynanen M, Knowlton RG, Parente MG, Chung LC, Chu ML, Uitto J. Human type VII collagen: genetic linkage of the gene (COL7A1) on chromosome 3 to dominant dystrophic epidermolysis bullosa. Am J7 Hum Genet 1991; 49:797-803.","journal-title":"Am J7 Hum Genet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1172\/JCI115680","article-title":"Genetic linkage of type VII collagen (COL7A1) to dominant dystrophic epidermolysis bullosa in families with abnormal anchoring fibrils","volume":"89","author":"Ryynanen, M.; Ryynanen, J.; Sollberg, S.; Iozzo, R.V.; Knowlton, R.G.; Uitto, J.","year":"1992","unstructured":"Ryynanen M, Ryynanen J, Sollberg S, Iozzo RV, Knowlton RG, Uitto J. Genetic linkage of type VII collagen (COL7A1) to dominant dystrophic epidermolysis bullosa in families with abnormal anchoring fibrils. Jf Clin Invest 1992;89:974-80.","journal-title":"Jf Clin Invest"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1111\/1523-1747.ep12658066","article-title":"Genetic linkage between the collagen VII (COL7A1) gene and the autosomal dominant form of dystrophic epidermolysis bullosa in two Dutch kindreds","volume":"99","author":"Gruis, N.A.; Bouwes Bavinck, J.N.; Steijlen, P.M.","year":"1992","unstructured":"Gruis NA, Bouwes Bavinck JN, Steijlen PM, et al. Genetic linkage between the collagen VII (COL7A1) gene and the autosomal dominant form of dystrophic epidermolysis bullosa in two Dutch kindreds. J Invest Dermatol 1992; 99:528-30.","journal-title":"J Invest Dermatol"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1136\/jmg.29.6.381","article-title":"Linkage of autosomal dominant dystrophic epidermolysis bullosa in three British families to the marker D3S2 close to the COL7A1 locus","volume":"29","author":"Al-Imara, L.; Richards, A.J.; Eady, R.A.J.; Leigh, I.M.; Farrall, M.; Pope, F.M.","year":"1992","unstructured":"Al-Imara L, Richards AJ, Eady RAJ, Leigh IM, Farrall M, Pope FM. Linkage of autosomal dominant dystrophic epidermolysis bullosa in three British families to the marker D3S2 close to the COL7A1 locus. J Med Genet 1992;29: 381-2.","journal-title":"J Med Genet"},{"key":"ref_13","first-page":"1032","article-title":"Genetic linkage of recessive dystrophic epidermolysis bullosa to the type VII collagen gene","volume":"90","author":"Hovnanian, A.; Duquesnoy, P.; Blanchet-Bardon, C.","year":"1992","unstructured":"Hovnanian A, Duquesnoy P, Blanchet-Bardon C, et al. Genetic linkage of recessive dystrophic epidermolysis bullosa to the type VII collagen gene. _7 Clin Invest 1992;90: 1032-6."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/ng1193-287","article-title":"A homozygous insertion-deletion in the type VII collagen gene (COL7A1) in Hallopeau-Siemens dystrophic epidermolysis bullosa","volume":"5","author":"Hilal, L.; Rochat, A.; Duquesnoy, P.","year":"1993","unstructured":"Hilal L, Rochat A, Duquesnoy P, et al. A homozygous insertion-deletion in the type VII collagen gene (COL7A1) in Hallopeau-Siemens dystrophic epidermolysis bullosa. Nature Genet 1993;5:287-93.","journal-title":"Nature Genet"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/ng0593-62","article-title":"A missense mutation in type VII collagen in two affected siblings with recessive dystrophic epidermolysis bullosa","volume":"4","author":"Christiano, A.M.; Greenspan, D.S.; Hoffman, G.G.","year":"1993","unstructured":"Christiano AM, Greenspan DS, Hoffman GG, et al. A missense mutation in type VII collagen in two affected siblings with recessive dystrophic epidermolysis bullosa. Nature Genet 1993;4:62-6.","journal-title":"Nature Genet"},{"key":"ref_16","first-page":"137887","article-title":"Recessive dystrophic epidermolysis bullosa: evidence for increased collagenase as a genetic characteristic in cell culture","volume":"148","author":"Bauer, E.A.; Eisen, A.Z.","year":"1978","unstructured":"Bauer EA, Eisen AZ. Recessive dystrophic epidermolysis bullosa: evidence for increased collagenase as a genetic characteristic in cell culture. J Exp Med 1978;148: 137887.","journal-title":"J Exp Med"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1172\/JCI110577","article-title":"Human skin collagenase in recessive dystrophic epidermolysis bullosa: purification of a mutant enzyme from fibroblast cultures","volume":"69","author":"Stricklin, P.G.; Welgus, H.G.; Bauer, E.A.","year":"1982","unstructured":"Stricklin PG, Welgus HG, Bauer EA. Human skin collagenase in recessive dystrophic epidermolysis bullosa: purification of a mutant enzyme from fibroblast cultures. Jr Clin Invest 1982;69:1373-83.","journal-title":"Jr Clin Invest"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1716","DOI":"10.1172\/JCI115489","article-title":"Exclusion of linkage between the collagenase gene and generalized recessive dystrophic epidermolysis bullosa phenotype","volume":"88","author":"Hovnanian, A.; Duquesnoy, P.; Amselem, S.","year":"1991","unstructured":"Hovnanian A, Duquesnoy P, Amselem S, et al. Exclusion of linkage between the collagenase gene and generalized recessive dystrophic epidermolysis bullosa phenotype. J Clin Invest 1991;88:1716-21.","journal-title":"J Clin Invest"},{"key":"ref_19","first-page":"503","article-title":"Exclusion of stromelysin-1, stromelysin-2, interstitial collagenase and fibronectin genes as the mutant loci in a family with recessive epidermolysis bullosa dystrophica and a form of cerebellar ataxia","volume":"89","author":"Colombe, M.; Gardella, R.; Zoppi, N.","year":"1992","unstructured":"Colombe M, Gardella R, Zoppi N, et al. Exclusion of stromelysin-1, stromelysin-2, interstitial collagenase and fibronectin genes as the mutant loci in a family with recessive epidermolysis bullosa dystrophica and a form of cerebellar ataxia. Hum Genet 1992;89:503-7.","journal-title":"Hum Genet"},{"key":"ref_20","first-page":"98590","article-title":"An improved method for prenatal diagnosis of genetic diseases by analysis of amplified DNA sequences","volume":"317","author":"Kogan, S.C.; Doherty, M.; Gitschier, J.","year":"1987","unstructured":"Kogan SC, Doherty M, Gitschier J. An improved method for prenatal diagnosis of genetic diseases by analysis of amplified DNA sequences. N Engl J Med 1987;317:98590.","journal-title":"N Engl J Med"},{"key":"ref_21","series-title":"Dermatology progress and perspectives. Proceedings of the 18th World Congress of Dermatology","first-page":"1159","article-title":"Chair's summary: prenatal diagnosis of skin diseases","author":"Eady, R.A.J.; Holbrook, K.A.; Blanchet-Bardon, C.; Anton-Lamprecht, I.","year":"1993","unstructured":"Eady RAJ, Holbrook KA, Blanchet-Bardon C, Anton-Lamprecht I. Chair's summary: prenatal diagnosis of skin diseases. In: Burgdorf WHC, Katz SI, eds. Dermatology progress and perspectives. Proceedings of the 18th World Congress of Dermatology. New York: Parthenon Publishing, 1993:1159-65."},{"key":"ref_22","first-page":"515","article-title":"Prenatal diagnosis of recessive dystrophic epidermolysis bullosa by analysis of intragenic type VII collagen PvuII polymorphism","volume":"100","author":"Hovnanian, A.; Hilal, L.; Blanchet-Bardon, C.","year":"1993","unstructured":"Hovnanian A, Hilal L, Blanchet-Bardon C, et al. Prenatal diagnosis of recessive dystrophic epidermolysis bullosa by analysis of intragenic type VII collagen PvuII polymorphism. 7 Invest Dermatol 1993;100:515A."},{"key":"ref_23","first-page":"482","article-title":"PCR-based detection of intragenic RFLPs in the human type VII collagen gene: applications to prenatal diagnosis of dystrophic epidermolysis bullosa","volume":"101","author":"Tamai, Y.; Zhang, X.; Christiano, A.M.; Hovnanian, A.; Uitto, J.","year":"1993","unstructured":"Tamai Y, Zhang X, Christiano AM, Hovnanian A, Uitto J. PCR-based detection of intragenic RFLPs in the human type VII collagen gene: applications to prenatal diagnosis of dystrophic epidermolysis bullosa. J Invest Dermatol 1993;101:482A.","journal-title":"J Invest Dermatol"},{"key":"ref_24","first-page":"1877","article-title":"CA repeat polymorphisms for human chromosome 3","volume":"58","author":"Garcia, D.K.; Sherman, S.; Leach, R.S.","year":"1991","unstructured":"Garcia DK, Sherman S, Leach RS, et al. CA repeat polymorphisms for human chromosome 3. Cytogenet Cell Genet 1991;58: 1877A.","journal-title":"Cytogenet Cell Genet"},{"key":"ref_25","first-page":"1","article-title":"Transmission electron microscopy","volume-title":"Methods in skin research","author":"Eady, R.A.J.","year":"1985","unstructured":"Eady RAJ. Transmission electron microscopy. In: Skerrow D, Skerrow CJ, eds. Methods in skin research. Chichester: John Wiley, 1985:1-36."},{"key":"ref_26","first-page":"17","article-title":"LH7: 2 monoclonal antibody detects type VII collagen in the basement membrane of ectodermally derived epithelia including skin","volume":"1","author":"Leigh, I.M.; Purkis, P.E.; Bruckner-Tuderman, L.","year":"1988","unstructured":"Leigh IM, Purkis PE, Bruckner-Tuderman L. LH7:2 monoclonal antibody detects type VII collagen in the basement membrane of ectodermally derived epithelia including skin. Epithelia 1988;1:17-29.","journal-title":"Epithelia"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/0014-4827(87)90121-2","article-title":"Monoclonal antibody GB3, a new tool for the study of human basement membranes and hemidesmosomes","volume":"170","author":"Verrando, P.; Pisani, A.; Hsi, B.L.","year":"1987","unstructured":"Verrando P, Pisani A, Hsi BL, et al. Monoclonal antibody GB3, a new tool for the study of human basement membranes and hemidesmosomes. Exp Cell Res 1987;170: 116-28.","journal-title":"Exp Cell Res"},{"key":"ref_28","first-page":"460","article-title":"Easy calculation of lod scores and genetic risks on small computers","volume":"36","author":"Lathrop, M.G.; Lalouel, J.M.","year":"1984","unstructured":"Lathrop MG, Lalouel JM. Easy calculation of lod scores and genetic risks on small computers. Am J Hum Genet 1984;36:460-5.","journal-title":"Am J Hum Genet"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1093\/hmg\/1.7.475","article-title":"The large non-collagenous domain (NC-1) of type VII collagen is amino-terminal and chimeric. Homology to cartilage matrix protein, the type III domains offibronectin and the A domains of von Willebrand factor","volume":"1","author":"Christiano, A.M.; Rosenbaum, L.M.; Chung-Honet, L.C.","year":"1992","unstructured":"Christiano AM, Rosenbaum LM, Chung-Honet LC, et al. The large non-collagenous domain (NC-1) of type VII collagen is amino-terminal and chimeric. Homology to cartilage matrix protein, the type III domains offibronectin and the A domains of von Willebrand factor. Hum Molec Genet 1992;1:475-81.","journal-title":"Hum Molec Genet"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1159\/000133440","article-title":"Localization of the human collagen gene COL7A1 to 3p2l.3 by fluorescence in situ hybridization","volume":"62","author":"Greenspan, D.S.; Byers, M.G.; Eddy, R.L.; Hoffman, G.G.; Shows, T.B.","year":"1993","unstructured":"Greenspan DS, Byers MG, Eddy RL, Hoffman GG, Shows TB. Localization of the human collagen gene COL7A1 to 3p2l.3 by fluorescence in situ hybridization. Cytogenet Cell Genet 1993;62:35-6.","journal-title":"Cytogenet Cell Genet"}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg.31.10.745","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T05:00:53Z","timestamp":1759726853000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg.31.10.745"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,10]]},"references-count":30,"journal-issue":{"issue":"10","published-online":{"date-parts":[[1994,10,1]]},"published-print":{"date-parts":[[1994,10]]}},"alternative-id":["10.1136\/jmg.31.10.745"],"URL":"https:\/\/doi.org\/10.1136\/jmg.31.10.745","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"type":"print","value":"0022-2593"},{"type":"electronic","value":"1468-6244"}],"subject":[],"published":{"date-parts":[[1994,10]]}}}