{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T03:40:02Z","timestamp":1759722002476,"version":"build-2065373602"},"reference-count":19,"publisher":"BMJ","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1991,12]]},"abstract":"<jats:p>The features of a child with Ehlers-Danlos syndrome type IV (EDS IV) resulting from a mutation in one COL3A1 allele were studied. The child was heterozygous for a G- to A-transition at the splice donor site of intron 41. It resulted in the splicing out of the exon 41 encoded sequence from alpha 1(III) mRNA and the deletion of 36 amino acids from glycine775 to lysine810 of the triple helical domain of alpha 1(III) chains of type III collagen. The amount of type III collagen in the dermis was only about 11% of normal. The child had the acrogeric form of EDS IV. He had the characteristic facies with a pinched nose, thin lips, and prominent eyes. These facial features, his aesthenic build, thin skin, prominent subcutaneous veins, and aged hands produced a 'cachectic' appearance. These features were evident in early childhood and worsened up to 12 1\/2 years when he was last reviewed. Spontaneous bruising, bleeding from the large bowel, constipation, and delayed gastric emptying were other features. In cross section, the dermal collagen fibrils were round and measured 93.3 +\/- 11.5 nm in diameter which was not significantly different from control values of 102.5 +\/- 13.4 nm. The serum type III procollagen amino-terminal propeptide level of 25.5 ng\/ml was within the normal age matched values of 15.5 +\/- 7.7 ng\/ml despite the low production of type III collagen by cultured fibroblasts. The child probably had a spontaneous new mutation in one COL3A1 allele as only normal sequences were obtained from the corresponding amplified region of the parent's leucocyte DNA.<\/jats:p>","DOI":"10.1136\/jmg.28.12.840","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T15:11:11Z","timestamp":1226329871000},"page":"840-845","source":"Crossref","is-referenced-by-count":8,"title":["Ehlers-Danlos syndrome type IV: phenotypic consequences of a splicing mutation in one COL3A1 allele."],"prefix":"10.1136","volume":"28","author":[{"given":"D O","family":"Sillence","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A A","family":"Chiodo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P E","family":"Campbell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W G","family":"Cole","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1991,12,1]]},"reference":[{"key":"ref_1","first-page":"285","article-title":"Type III collagen mutations in Ehlers-Danlos syndrome type IV and other related disorders. Clin Exp Dermatol","volume":"13","author":"Pope, F.M.; Nicholls, A.C.; Narcisi, P.","year":"1988","unstructured":"Pope FM, Nicholls AC, Narcisi P, et al. Type III collagen mutations in Ehlers-Danlos syndrome type IV and other related disorders. Clin Exp Dermatol 1988;13:285-302."},{"key":"ref_2","first-page":"180","volume":"73","year":"1980","unstructured":"Pope FM, Nicholls AC, Jones PM, Wells RS, Lawrence DJ. EDS IV (acrogeria): new autosomal dominant and recessive types. J R Soc Med 1980;73:180-6.","journal-title":"Soc Med"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/BF00273196","article-title":"Clinical and ultrastructural heterogeneity of type IV Ehlers-Danlos syndrome","volume":"47","author":"Byers, P.H.; Holbrook, K.A.; McGillivray, B.; MacLeod, P.M.; Lowry, R.B.","year":"1979","unstructured":"Byers PH, Holbrook KA, McGillivray B, MacLeod PM, Lowry RB. Clinical and ultrastructural heterogeneity of type IV Ehlers-Danlos syndrome. Hum Genet 1979;47:141-50.","journal-title":"Hum Genet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0741-5214(87)90133-9","article-title":"Spontaneous arterial perforation: the Ehlers-Danlos specter","volume":"5","author":"Cikrit, D.F.; Miles, J.H.; Silver, D.","year":"1987","unstructured":"Cikrit DF, Miles JH, Silver D. Spontaneous arterial perforation: the Ehlers-Danlos specter. J Vasc Surg 1987;5:248-55.","journal-title":"J Vasc Surg"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"462","DOI":"10.3171\/jns.1987.66.3.0462","article-title":"Spontaneous carotid-cavernous fistula and multiple arterial dissections in type IV Ehlers-Danlos syndrome","volume":"66","author":"Lach, B.; Nair, S.G.; Russell, N.A.; Benoit, B.G.","year":"1987","unstructured":"Lach B, Nair SG, Russell NA, Benoit BG. Spontaneous carotid-cavernous fistula and multiple arterial dissections in type IV Ehlers-Danlos syndrome. J Neurosurg 1987;66:462-7.","journal-title":"J Neurosurg"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1177\/014107688307600614","article-title":"Type III collagen deficiency with normal phenotype","volume":"76","author":"Pope, F.M.; Nicholls, A.C.; Dorrance, D.E.; Child, A.H.; Narcisi, P.","year":"1983","unstructured":"Pope FM, Nicholls AC, Dorrance DE, Child AH, Narcisi P. Type III collagen deficiency with normal phenotype. J R Soc Med 1983;76:518-20.","journal-title":"J R Soc Med"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"17070","DOI":"10.1016\/S0021-9258(17)44870-8","article-title":"A base substitution at a splice site in the COL3A1 gene causes exon skipping and generates abnormal type III procollagen in a patient with Ehlers-Danlos syndrome type","volume":"265","author":"Cole, W.G.; Chiodo, A.A.; Lamande, SR","year":"1990","unstructured":"Cole WG, Chiodo AA, Lamande SR, et al. A base substitution at a splice site in the COL3A1 gene causes exon skipping and generates abnormal type III procollagen in a patient with Ehlers-Danlos syndrome type IV. J Biol Chem 1990; 265:17070-7.","journal-title":"IV. J Biol Chem"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1136\/jmg.24.11.698","article-title":"The clinical features of Ehlers-Danlos syndrome type VII due to a deletion of 24 amino acids from the pro-al(I) chain of type I procollagen","volume":"24","author":"Cole, W.G.; Evans, R.; Sillence, D.O.","year":"1987","unstructured":"Cole WG, Evans R, Sillence DO. The clinical features of Ehlers-Danlos syndrome type VII due to a deletion of 24 amino acids from the pro-al(I) chain of type I procollagen. J Med Genet 1987;24:698-701.","journal-title":"J Med Genet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1111\/j.1365-2362.1989.tb00242.x","article-title":"Low levels of serum type III procollagen aminoterminal propeptide confirmed type III collagen deficiency in patients without typical clinical symptoms of Ehlers-Danlos type IV","volume":"19","author":"Dyne, K.M.; Zanaboni, G.; Annoni, G.; De Agostini, M.P.; Cetta, G.","year":"1989","unstructured":"Dyne KM, Zanaboni G, Annoni G, De Agostini MP, Cetta G. Low levels of serum type III procollagen aminoterminal propeptide confirmed type III collagen deficiency in patients without typical clinical symptoms of Ehlers-Danlos type IV. Eur Clin Invest 1989;19:362-6.","journal-title":"Eur Clin Invest"},{"issue":"28","key":"ref_10","first-page":"228","article-title":"Variants of the Ehlers-Danlos syndrome. Clinical, biochemical, haematological, and chromosomal features of 100 patients","volume":"1969","author":"Beighton, P.; Price, A.; Lord, J.","unstructured":"Beighton P, Price A, Lord J. Variants of the Ehlers-Danlos syndrome. Clinical, biochemical, haematological, and chromosomal features of 100 patients. Ann Rheum Dis 1969;28:228-42.","journal-title":"Ann Rheum Dis"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1042\/bj2480483","article-title":"Platelet-reactive sites in collagen. Collagens I and III possess different aggregatory sites","volume":"248","author":"Morton, L.F.; Fitzsimmons, C.M.; Rauterberg, J.; Bames, M.J.","year":"1987","unstructured":"Morton LF, Fitzsimmons CM, Rauterberg J, Bames MJ. Platelet-reactive sites in collagen. Collagens I and III possess different aggregatory sites. 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Connect Tissue Res (in press).","journal-title":"Connect Tissue Res"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"6226","DOI":"10.1016\/S0021-9258(18)68776-9","article-title":"Ehlers-Danlos syndrome type IV: a multi-exon deletion in one of the two COL3A1 alleles affecting structure, stability and processing of type III procollagen","volume":"263","author":"Superti-Furga, A.; Gugler, E.; Gitzelmann, R.; Steinmann, B.","year":"1988","unstructured":"Superti-Furga A, Gugler E, Gitzelmann R, Steinmann B. Ehlers-Danlos syndrome type IV: a multi-exon deletion in one of the two COL3A1 alleles affecting structure, stability and processing of type III procollagen. J Biol Chem 1988;263:6226-32.","journal-title":"J Biol Chem"},{"key":"ref_15","first-page":"336","article-title":"Altered secretion of type III procollagen in a form of type IV Ehlers-Danlos syndrome","volume":"44","year":"1981","unstructured":"Byers PH, Holbrook KA, Barsh GS, Smith LT, Bornstein MD. Altered secretion of type III procollagen in a form of type IV Ehlers-Danlos syndrome. Lab Invest 1981;44:336-41.","journal-title":"Lab Invest"},{"key":"ref_16","first-page":"971","article-title":"Lung collagen in type IV Ehlers-Danlos syndrome: ultrastructural and biochemical studies","volume":"122","author":"Clark, J.G.; Kuhn, C.; Uitto, J.","year":"1980","unstructured":"Clark JG, Kuhn C, Uitto J. Lung collagen in type IV Ehlers-Danlos syndrome: ultrastructural and biochemical studies. Am Rev Respir Dis 1980;122:971-8.","journal-title":"Am Rev Respir Dis"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1016\/S0021-9258(18)94192-X","article-title":"A single base mutation that substitutes serine for glycine 790 of the al(III) chain of type III procollagen exposes an arginine and causes Ehlers-Danlos syndrome","volume":"264","author":"Tromp, G.; Kuivaniemi, H.; Shikata, H.; Prockop, D.J.","year":"1989","unstructured":"Tromp G, Kuivaniemi H, Shikata H, Prockop DJ. A single base mutation that substitutes serine for glycine 790 of the al(III) chain of type III procollagen exposes an arginine and causes Ehlers-Danlos syndrome IV. J Biol Chem 1989;264:1349-52.","journal-title":"IV. J Biol Chem"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"19313","DOI":"10.1016\/S0021-9258(19)47303-1","article-title":"Single base mutation in the type III procollagen gene that converts the codon for glycine 883 to aspartate in a mild variant of Ehlers-Danlos syndrome","volume":"264","author":"Tromp, G.; Kuivaniemi, H.; Stolle, C.; Pope, F.M.; Prockop, D.J.","year":"1989","unstructured":"Tromp G, Kuivaniemi H, Stolle C, Pope FM, Prockop DJ. Single base mutation in the type III procollagen gene that converts the codon for glycine 883 to aspartate in a mild variant of Ehlers-Danlos syndrome IV. J Biol Chem 1989;264:19313-7.","journal-title":"IV. J Biol Chem"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"12067","DOI":"10.1016\/S0021-9258(19)38508-4","article-title":"Identical G+' to A mutations in three different introns of the type III procollagen gene (COL3Al) produce different patterns of RNA splicing in three variants of EhlersDanlos syndrome IV","volume":"265","author":"Kuivaniemi, H.; Kontusaari, S.; Tromp, G.; Zhao, M.; Sabol, C.; Prockop, D.J.","year":"1990","unstructured":"Kuivaniemi H, Kontusaari S, Tromp G, Zhao M, Sabol C, Prockop DJ. Identical G+' to A mutations in three different introns of the type III procollagen gene (COL3Al) produce different patterns of RNA splicing in three variants of EhlersDanlos syndrome IV. J Biol Chem 1990;265:12067-74.","journal-title":"J Biol Chem"}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg.28.12.840","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T03:16:02Z","timestamp":1759720562000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg.28.12.840"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1991,12]]},"references-count":19,"journal-issue":{"issue":"12","published-online":{"date-parts":[[1991,12,1]]},"published-print":{"date-parts":[[1991,12]]}},"alternative-id":["10.1136\/jmg.28.12.840"],"URL":"https:\/\/doi.org\/10.1136\/jmg.28.12.840","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"type":"print","value":"0022-2593"},{"type":"electronic","value":"1468-6244"}],"subject":[],"published":{"date-parts":[[1991,12]]}}}