{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T05:12:15Z","timestamp":1773292335928,"version":"3.50.1"},"reference-count":29,"publisher":"BMJ","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1998,10]]},"abstract":"<jats:p>Ehlers-Danlos syndrome (EDS) is a heterogeneous group of connective tissue disorders. Recently mutations have been found in the genes for type V collagen in a small number of people with the most common forms of EDS, types I and II. Here we characterise a COL5A2 mutation in an EDS II family. Cultured dermal fibroblasts obtained from an affected subject synthesised abnormal type V collagen. Haplotype analysis excluded COL5A1 but was concordant with COL5A2 as the disease locus. The entire open reading frame of the COL5A2 cDNA was directly sequenced and a single base mutation detected. It substituted a glycine residue within the triple helical domain (G934R) of alpha2(V) collagen, typical of the dominant negative changes in other collagens, which cause various other inherited connective tissue disorders. All three affected family members possessed the single base change, which was absent in 50 normal chromosomes.<\/jats:p>","DOI":"10.1136\/jmg.35.10.846","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T15:37:21Z","timestamp":1226331441000},"page":"846-848","source":"Crossref","is-referenced-by-count":66,"title":["A single base mutation in COL5A2 causes Ehlers-Danlos syndrome type II."],"prefix":"10.1136","volume":"35","author":[{"given":"A J","family":"Richards","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Martin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A C","family":"Nicholls","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J B","family":"Harrison","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F M","family":"Pope","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N P","family":"Burrows","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1998,10,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1093\/hmg\/5.11.1733","article-title":"A splice-junction mutation in the region of COL5A1 that codes for the carboxyl propeptide of pro-au (V) chains results in the gravis form of Ehlers-Danlos syndrome (type I)","volume":"5","author":"Wenstrup, R.J.; Langland, G.T.; Willing, M.C.; Dsouza, V.N.; Cole, W.G.","year":"1996","unstructured":"Wenstrup RJ, Langland GT, Willing MC, Dsouza VN, Cole WG. A splice-junction mutation in the region of COL5A1 that codes for the carboxyl propeptide of pro-au (V) chains results in the gravis form of Ehlers-Danlos syndrome (type I). Hum Mol Genet 1996;5:1733-6.","journal-title":"Hum Mol Genet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1136\/jmg.33.11.940","article-title":"An exon skipping mutation of a type V collagen gene (COL5A1) in Ehlers-Danlos syndrome","volume":"33","author":"Nicholls, A.C.; Oliver, J.E.; McCarron, S.; Harrison, J.B.; Greenspan, D.S.; Pope, F.M.","year":"1996","unstructured":"Nicholls AC, Oliver JE, McCarron S, Harrison JB, Greenspan DS, Pope FM. An exon skipping mutation of a type V collagen gene (COL5A1) in Ehlers-Danlos syndrome. iMed Genet 1996;33:940-6.","journal-title":"iMed Genet"},{"key":"ref_3","first-page":"547","article-title":"Mutations in the COL5A1 gene are causal in the Ehlers-Danlos syndromes I","volume":"60","author":"A, De Paepe; L, Nuytink; I, Hausser; I, Anton-Lamprecht; JM, Naeyaert","year":"1997","unstructured":"De Paepe A, Nuytink L, Hausser I, Anton-Lamprecht I, Naeyaert JM. Mutations in the COL5A1 gene are causal in the Ehlers-Danlos syndromes I and II. Am J Hum Genet 1997;60:547-54.","journal-title":"and II. Am J Hum Genet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1093\/hmg\/7.2.249","article-title":"Mutations of the a2(V) chain of type V collagen impair matrix assembly and produces Ehlers-Danlos syndrome type","volume":"7","author":"Michalickova, K.; Susic, M.; Willing, M.C.; Wenstrup, R.J.; Cole, W.G.","year":"1998","unstructured":"Michalickova K, Susic M, Willing MC, Wenstrup RJ, Cole WG. Mutations of the a2(V) chain of type V collagen impair matrix assembly and produces Ehlers-Danlos syndrome type I. Hum Mol Genet 1998;7:249-55.","journal-title":"I. Hum Mol Genet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1083\/jcb.108.1.191","article-title":"Cartilage contains mixed fibrils of collagen types II, IX and","volume":"108","author":"Mendler, M.; Eich-Bender, S.G.; Vaughan, L.; Winterhalter, K.H.; Bruckner, P.","year":"1989","unstructured":"Mendler M, Eich-Bender SG, Vaughan L, Winterhalter KH, Bruckner P. Cartilage contains mixed fibrils of collagen types II, IX and XI._J Cell Biol 1989;108:191-7.","journal-title":"XI._J Cell Biol"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2814","DOI":"10.1096\/fasebj.5.13.1916105","article-title":"The collagen family of proteins","volume":"5","author":"M, Van Der Rest; R, Garrone","year":"1991","unstructured":"Van Der Rest M, Garrone R. The collagen family of proteins. FASEBJ 1991;5:2814-23.","journal-title":"FASEBJ"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1083\/jcb.121.5.1181","article-title":"Type V collagen: molecular structure and fibrillar organization of chicken at1 (V) NH2-terminal domain, a putative regulator of corneal fibrillogenesis","volume":"121","author":"Linsenmayer, T.F.; Gibney, E.; Igoe, F.","year":"1993","unstructured":"Linsenmayer TF, Gibney E, Igoe F, et al. Type V collagen: molecular structure and fibrillar organization of chicken at1 (V) NH2-terminal domain, a putative regulator of corneal fibrillogenesis. Jf Cell Biol 1993;121:1181-9.","journal-title":"Jf Cell Biol"},{"issue":"14","key":"ref_8","first-page":"515","article-title":"Another look at collagen V and XI molecules","volume":"1995","author":"Fichard, A.; Kleman, J.P.; Ruggiero, F.","unstructured":"Fichard A, Kleman JP, Ruggiero F. Another look at collagen V and XI molecules. Matrix Biol 1995,14:515-31.","journal-title":"Matrix Biol"},{"issue":"73","key":"ref_9","first-page":"2579","article-title":"Fetal membrane collagens: identification of two new","volume-title":"collagen o chains. Proc NatlAcad Sci USA","volume":"1976","author":"Burgeson, R.E.; El Adli, F.A.; Kaitila, II, Hollister; D.W.","unstructured":"Burgeson RE, El Adli FA, Kaitila II, Hollister DW. Fetal membrane collagens: identification of two new collagen o chains. Proc NatlAcad Sci USA 1976,73:2579-83."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S0174-173X(83)80002-8","article-title":"Extraction, isolation and characterization of neutral salt soluble type V collagen from fetal calf skin","volume":"3","author":"Elstow, S.F.; Weiss, J.B.","year":"1983","unstructured":"Elstow SF, Weiss JB. Extraction, isolation and characterization of neutral salt soluble type V collagen from fetal calf skin. Collagen Rel Res 1983;3:181-94.","journal-title":"Collagen Rel Res"},{"key":"ref_11","first-page":"555","article-title":"Characterization of the tissue form of type V collagen from chick bone","volume":"260","author":"Broek, D.L.; Madri, J.; Eikenberry, E.F.; Brodsky, B.","year":"1991","unstructured":"Broek DL, Madri J, Eikenberry EF, Brodsky B. Characterization of the tissue form of type V collagen from chick bone. JfBiol Chem 1991;260:555-62.","journal-title":"JfBiol Chem"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1083\/jcb.135.5.1415","article-title":"Reduction of type V collagen using a dominant-negative strategy alters the regulation of fibrillogenesis and results in the loss of corneal-specific fibril morphology","volume":"135","author":"Marchant, J.K.; Hahn, R.A.; Linsenmayer, T.F.; Birk, D.E.","year":"1996","unstructured":"Marchant JK, Hahn RA, Linsenmayer TF, Birk DE. Reduction of type V collagen using a dominant-negative strategy alters the regulation of fibrillogenesis and results in the loss of corneal-specific fibril morphology. Jf Cell Biol 1996;135: 1415-26.","journal-title":"Jf Cell Biol"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/0092-8674(95)90492-1","article-title":"A fibrillar collagen gene, COLl lAl, is essential for skeletal morphogenesis","volume":"80","author":"Li, Y.; Lacerada, D.A.; Warman, M.L.","year":"1995","unstructured":"Li Y, Lacerada DA, Warman ML, et al. A fibrillar collagen gene, COLl lAl, is essential for skeletal morphogenesis. Cell 1995;80:423-30.","journal-title":"Cell"},{"key":"ref_14","first-page":"3825","article-title":"Assembly of cartilage collagen fibrils is disrupted by overexpression of normal type II collagen","volume-title":"transgenic mice. Proc Natl Acad Sci USA","volume":"90","author":"Garofalo, S.; Metsaranta, M.; Ellard, J.","year":"1993","unstructured":"Garofalo S, Metsaranta M, Ellard J, et al. Assembly of cartilage collagen fibrils is disrupted by overexpression of normal type II collagen in transgenic mice. Proc Natl Acad Sci USA 1993;90:3825-9."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2627","DOI":"10.1016\/S0021-9258(18)34970-6","article-title":"Comparison of collagen types in adult and fetal bovine corneas","volume":"257","author":"Tseng, S.C.G.; Smuckler, D.; Stern, R.","year":"1982","unstructured":"Tseng SCG, Smuckler D, Stern R. Comparison of collagen types in adult and fetal bovine corneas. _7 Biol Chem 1982; 257:2627-33.","journal-title":"_7 Biol Chem"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1242\/jcs.94.2.371","article-title":"Type V collagen synthesis and deposition by chicken embryo corneal fibroblasts in vitro","volume":"94","author":"McLaughlin, J.S.; Linsenmayer, T.F.; Birk, D.E.","year":"1989","unstructured":"McLaughlin JS, Linsenmayer TF, Birk DE. Type V collagen synthesis and deposition by chicken embryo corneal fibroblasts in vitro. _7 Cell Sci 1989;94:371-9.","journal-title":"_7 Cell Sci"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/0888-7543(95)80021-D","article-title":"COL5Al: fine genetic mapping and exclusion as candidate gene in families with nail-patella syndrome, tuberose sclerosis 1, hereditary hemorrhagic telangiectasia and Ehlers-Danlos syndrome type II","volume":"25","author":"Greenspan, D.S.; Northrup, H.; Au, K.S.","year":"1995","unstructured":"Greenspan DS, Northrup H, Au KS, et al. COL5Al: fine genetic mapping and exclusion as candidate gene in families with nail-patella syndrome, tuberose sclerosis 1, hereditary hemorrhagic telangiectasia and Ehlers-Danlos syndrome type II. Genomics 1995;25:737-9.","journal-title":"Genomics"},{"key":"ref_18","first-page":"729","article-title":"Targeted disruption of decorin leads to abnormal collagen fibril morphology and skin fragility..7 Cell Biol","volume":"136","author":"Danielson, K.G.; Baribault, H.; Holmes, D.F.; Graham, H.; Kadler, K.E.; Iozzo, R.V.","year":"1997","unstructured":"Danielson KG, Baribault H, Holmes DF, Graham H, Kadler KE, Iozzo RV. Targeted disruption of decorin leads to abnormal collagen fibril morphology and skin fragility..7 Cell Biol 1997;136:729-43."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/ng0997-104","article-title":"Tenascin-X deficiency is associated with Ehlers-Danlos syndrome","volume":"17","author":"Burch, G.H.; Gong, Y.; Liu, W.","year":"1997","unstructured":"Burch GH, Gong Y, Liu W, et al. Tenascin-X deficiency is associated with Ehlers-Danlos syndrome. Nat Genet 1997; 17:104-8.","journal-title":"Nat Genet"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/316363a0","article-title":"Subtle structural alterations in the chains of type I procollagen produce osteogenesis imperfecta type II","volume":"316","author":"Bonadio, J.; Byers, P.H.","year":"1985","unstructured":"Bonadio J, Byers PH. Subtle structural alterations in the chains of type I procollagen produce osteogenesis imperfecta type II. Nature 1985;316:363-6.","journal-title":"Nature"},{"key":"ref_21","first-page":"5256","article-title":"position +5 of a splice donor site causes skipping of the preceding exon in the type III procollagen transcripts of a patient with Ehlers-Danlos syndrome type","volume":"266","author":"Lee, B.; Vitale, E.; Superti-Furga, A.; Steinmann, B.; Ramirez, F.","year":"1991","unstructured":"Lee B, Vitale E, Superti-Furga A, Steinmann B, Ramirez F. G to T transversion at position +5 of a splice donor site causes skipping of the preceding exon in the type III procollagen transcripts of a patient with Ehlers-Danlos syndrome type IV. _7 Biol Chem 1991;266:5256-9.","journal-title":"G to T transversion; IV. _7 Biol Chem"},{"key":"ref_22","first-page":"407","article-title":"Physical mapping by PFGE localizes the COL3A1 and COL5A2 genes to a 35-kb region on human chromosome 2","volume-title":"Genomics","volume":"8","author":"Cutting, G.R.; McGinniss, M.J.; Kasch, L.M.; Tsipouras, P.; Antonarakis, S.E.","year":"1990","unstructured":"Cutting GR, McGinniss MJ, Kasch LM, Tsipouras P, Antonarakis SE. Physical mapping by PFGE localizes the COL3A1 and COL5A2 genes to a 35-kb region on human chromosome 2. 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Science 1996;274:540-6.","journal-title":"Science"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1002\/(SICI)1098-1004(1997)9:4<300::AID-HUMU2>3.0.CO;2-9","article-title":"Mutations in fibrillar collagens (type I, II, III and XI, fibril-associated collagen (type IX), and network-forming collagen (type X) cause a spectrum of diseases of bone, cartilage and blood vessels","volume":"9","author":"Kuivaniemi, H.; Tromp, G.; Prockop, D.J.","year":"1997","unstructured":"Kuivaniemi H, Tromp G, Prockop DJ. Mutations in fibrillar collagens (type I, II, III and XI, fibril-associated collagen (type IX), and network-forming collagen (type X) cause a spectrum of diseases of bone, cartilage and blood vessels. 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A family with Stickler syndrome type 2 has a mutation in the COLI lAI gene resulting in the substitution of glycine 97 by valine in al (XI) collagen. Hum Mol Genet 1996,5:1339-43.","journal-title":"Hum Mol Genet"},{"key":"ref_28","first-page":"571","article-title":"Keratoconus and the Ehlers-Danlos syndrome: a new aspect of keratoconus","volume":"1","author":"Robertson, I.","year":"1975","unstructured":"Robertson I. Keratoconus and the Ehlers-Danlos syndrome: a new aspect of keratoconus. Med JAust 1975;1:571-3.","journal-title":"Med JAust"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/ng0195-31","article-title":"Targeted mutation in the col5a2 gene reveals a regulatory role for type V collagen during matrix assembly","volume":"9","author":"Andrikopoulos, K.; Liu, X.; Keene, D.R.; Jaenisch, R.; Ramirez, F.","year":"1995","unstructured":"Andrikopoulos K, Liu X, Keene DR, Jaenisch R, Ramirez F. Targeted mutation in the col5a2 gene reveals a regulatory role for type V collagen during matrix assembly. Nat Genet 1995;9:31-6.","journal-title":"Nat Genet"}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg.35.10.846","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T22:23:28Z","timestamp":1760739808000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg.35.10.846"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,10]]},"references-count":29,"journal-issue":{"issue":"10","published-online":{"date-parts":[[1998,10,1]]},"published-print":{"date-parts":[[1998,10]]}},"alternative-id":["10.1136\/jmg.35.10.846"],"URL":"https:\/\/doi.org\/10.1136\/jmg.35.10.846","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"value":"0022-2593","type":"print"},{"value":"1468-6244","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,10]]}}}