{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T16:22:45Z","timestamp":1775146965726,"version":"3.50.1"},"reference-count":20,"publisher":"BMJ","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1984,6]]},"abstract":"<jats:p>Marfan syndrome is an autosomal dominant condition with varying phenotypic manifestations. Affected persons are usually heterozygotes. A family is presented in which the gene for this syndrome is segregating in a large number of members. Two sibs suffered from unusually severe, identical, and fatal manifestations from birth, their parents having mild cardiovascular and somatic symptoms common in Marfan syndrome. Investigation of collagen biosynthesis in fibroblasts revealed no abnormalities in fibronectin and procollagen I and III synthesis and secretion or in the procollagen to collagen conversion. We suggest that these two sibs are examples of homozygosity for the Marfan syndrome gene, based on the large number of affected members, the absence of additional consanguinity, manifestation of the syndrome in both parents, and the severity of the disease in the two sibs.<\/jats:p>","DOI":"10.1136\/jmg.21.3.173","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T15:09:16Z","timestamp":1226329756000},"page":"173-177","source":"Crossref","is-referenced-by-count":18,"title":["Homozygosity for autosomal dominant Marfan syndrome."],"prefix":"10.1136","volume":"21","author":[{"given":"J","family":"Chemke","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"Nisani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Feigl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"Garty","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Cooper","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y","family":"B\u00e5rash","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D","family":"Duksin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1984,6,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1056\/NEJM197904053001406","article-title":"The Marfan syndrome: diagnosis and management","volume":"300","author":"Pyeritz, R.E.; McKusick, V.A.","year":"1979","unstructured":"Pyeritz RE, McKusick VA. The Marfan syndrome: diagnosis and management. N Engl J Med 1979;300: 772-7.","journal-title":"N Engl J Med"},{"key":"ref_2","first-page":"155","article-title":"Clinical variability in the Marfan syndrome(s). Birth Defects defect in this condition. We propose that the two severely affected sibs represent examples of homozygosity for the Marfan gene. This assumption is based on the severe and","volume":"5","author":"Pyeritz, R.E.; Murphy, E.A.; McKusick, V.A.","year":"1979","unstructured":"Pyeritz RE, Murphy EA, McKusick VA. Clinical variability in the Marfan syndrome(s). Birth Defects defect in this condition. We propose that the two severely affected sibs represent examples of homozygosity for the Marfan gene. This assumption is based on the severe and 1979;XV(5B):155-78."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1016\/S0021-9258(19)75191-6","article-title":"Impaired conversion of procollagen to collagen by fibroblasts and bone treated with tunicamycin, an inhibitor of protein glycosylation","volume":"252","author":"Duksin, D.; Bornstein, P.","year":"1977","unstructured":"Duksin D, Bornstein P. Impaired conversion of procollagen to collagen by fibroblasts and bone treated with tunicamycin, an inhibitor of protein glycosylation. JBiol Chem 1977;252:955-62.","journal-title":"JBiol Chem"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3105","DOI":"10.1016\/S0021-9258(19)81080-3","article-title":"Relationship of the structure and biological activity of the natural homologues of tunicamycin","volume":"257","author":"Duksin, D.; Mahoney, W.C.","year":"1982","unstructured":"Duksin D, Mahoney WC. Relationship of the structure and biological activity of the natural homologues of tunicamycin. J Biol Chem 1982;257:3105-9.","journal-title":"J Biol Chem"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1056\/NEJM198110223051711","article-title":"Basic defects in the Marfan syndrome","volume":"305","author":"Pyeritz, R.E.; McKusick, V.A.","year":"1981","unstructured":"Pyeritz RE, McKusick VA. Basic defects in the Marfan syndrome. N Engl J Med 1981;305:1011-2.","journal-title":"N Engl J Med"},{"key":"ref_6","article-title":"and mentioned by McKusick, in which there weie some subjects much more severely affected born to first cousin parents.18","unstructured":"and mentioned by McKusick, in which there weie some subjects much more severely affected born to first cousin parents.18"},{"key":"ref_7","article-title":"Human genetics. Problems and approaches","author":"Vogel, F.; Motulsky, A.G.","year":"1979","unstructured":"Vogel F, Motulsky AG. Human genetics. Problems and approaches. New York: Springer-Verlag, 1979."},{"key":"ref_8","first-page":"97","article-title":"The production of lysyl oxidase by human fibroblasts in cultUre","volume":"149","author":"Layman, D.L.; Narayanan, A.S.; Martin, G.R.","year":"1972","unstructured":"Layman DL, Narayanan AS, Martin GR. The production of lysyl oxidase by human fibroblasts in cultUre. Arch Biochem Biophys 1972;149:97-101. However, other possible genetic mechanisms have to be considered, even though none can be proven owing to the lack of a specific detectable abnormality of collagen. Fried and Krakowski19 postulated","journal-title":"Arch Biochem Biophys; However, other possible genetic mechanisms have to be considered, even though none can be proven owing to the lack of a specific detectable abnormality of collagen. Fried and Krakowski19 postulated"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/0009-8981(68)90062-4","article-title":"Collagen metabolism in Marfan's syndrome","volume":"21","year":"1968","unstructured":"Laitinen 0, Uitto J, Livanainen M, Hannuksela M, Kivirikko KI. Collagen metabolism in Marfan's syndrome. Clin Chim Acta 1968;21:321-6.","journal-title":"Clin Chim Acta"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1038\/245264a0","article-title":"Collagen in Marfan syndrome is abnormally soluble","volume":"245","author":"Priest, R.E.; Moinuddin, J.F.; Priest, J.H.","year":"1973","unstructured":"Priest RE, Moinuddin JF, Priest JH. Collagen in Marfan syndrome is abnormally soluble. Nature 1973;245:264-6.","journal-title":"Nature"},{"key":"ref_11","first-page":"467","article-title":"Skin collagen in idiopathic adolescent scoliosis and Marfan's syndrome","volume":"51","author":"Francis, M.J.O.; Sanderson, M.C.; Smith, R.","year":"1976","unstructured":"Francis MJO, Sanderson MC, Smith R. Skin collagen in idiopathic adolescent scoliosis and Marfan's syndrome. Clin Sci Mol Med 1976;51:467-74.","journal-title":"Clin Sci Mol Med"},{"key":"ref_12","first-page":"150","article-title":"presented here, the parents are first cousins and both patients had a similar disease. Therefore, it could be assumed that the patients are homozygous for an autosomal recessive gene. The parents would thus be Biochem Biophys","volume":"32","year":"1968","unstructured":"presented here, the parents are first cousins and both patients had a similar disease. Therefore, it could be assumed that the patients are homozygous for an autosomal recessive gene. The parents would thus be Biochem Biophys Res Commun 1968;32:150-4.","journal-title":"Res Commun"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2428","DOI":"10.1172\/JCI107433","article-title":"Synthesis and degradation of hyaluronic acid in the cultured fibroblasts of Marfan's syndrome","volume":"52","author":"Lamberg, S.I.; Dorfman, A.","year":"1973","unstructured":"Lamberg SI, Dorfman A. Synthesis and degradation of hyaluronic acid in the cultured fibroblasts of Marfan's syndrome. J Clin Invest 1973;52:2428-33.","journal-title":"J Clin Invest"},{"key":"ref_14","first-page":"12199","article-title":"Cell-free synthesis of heterozygous and mildly affected. Another genetic model could be the presence of double dominant heterozygosity in both patients. Each parent would be heterozygous for an autohyaluronic acid in Marfan syndrome","volume":"254","author":"Appel, A.; Horwitz, A.L.; Dorfman, A.","year":"1979","unstructured":"Appel A, Horwitz AL, Dorfman A. Cell-free synthesis of heterozygous and mildly affected. Another genetic model could be the presence of double dominant heterozygosity in both patients. Each parent would be heterozygous for an autohyaluronic acid in Marfan syndrome. J Biol Chem 1979; 254:12199-203.","journal-title":"J Biol Chem"},{"key":"ref_15","article-title":"Case report and study of collagen metabolism in Marfan's syndrome. Klin Wochenschr 1981; 59: 83-90. somal dominant gene for a different type of abnormal collagen at different loci, and their offspring would thus be heterozygotes for each one of these genes. Mutations at different","author":"Halbritter, R.; Aumailley, M.; Rackwitz, R.; Kreig, T.; Muller, P.K.","unstructured":"Halbritter R, Aumailley M, Rackwitz R, Kreig T, Muller PK. Case report and study of collagen metabolism in Marfan's syndrome. Klin Wochenschr 1981;59:83-90. somal dominant gene for a different type of abnormal collagen at different loci, and their offspring would thus be heterozygotes for each one of these genes. Mutations at different loci, with alterations of"},{"key":"ref_16","first-page":"645","article-title":"Aortic aneurism in Marfan's syndrome: changes in the ultrastructure and composition of collagen","volume":"129","author":"Scheck, M.; Siegal, R.C.; Parker, J.; Chang, Y.H.; Fu, J.C.C.","year":"1979","unstructured":"Scheck M, Siegal RC, Parker J, Chang YH, Fu JCC. Aortic aneurism in Marfan's syndrome: changes in the ultrastructure and composition of collagen. J Anat 1979; 129:645-57.","journal-title":"J Anat"},{"key":"ref_17","first-page":"988","article-title":"The different subunits of collagen, are potentially possible, even though they have not been demonstrated so far. Until further knowledge is obtained on a specific Marfan syndrome: a deficiency in chemically stable collagen cross-links","volume":"305","author":"Boucek, R.J.; Noble, N.L.; Gunja-Smith, Z.; Butler, W.T.","year":"1981","unstructured":"Boucek RJ, Noble NL, Gunja-Smith Z, Butler WT. The different subunits of collagen, are potentially possible, even though they have not been demonstrated so far. Until further knowledge is obtained on a specific Marfan syndrome: a deficiency in chemically stable collagen cross-links. N Engl J Med 1981;305:988-91.","journal-title":"N Engl J Med"},{"key":"ref_18","first-page":"7745","article-title":"Marfan syndrome: abnormal a2 chain","volume-title":"type I collagen. Proc Nat! Acad Sci USA","volume":"78","author":"Byers, P.H.; Siegal, R.C.; Peterson, K.E.","year":"1981","unstructured":"Byers PH, Siegal RC, Peterson KE, et al. Marfan syndrome: abnormal a2 chain in type I collagen. Proc Nat! Acad Sci USA 1981;78:7745-9."},{"key":"ref_19","year":"1972","unstructured":"St Louis: Mosby, 1972."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1136\/jmg.14.5.359","article-title":"Probable autosomal recessive Marfan syndrome","volume":"14","author":"Fried, K.; Krakowsky, D.","year":"1977","unstructured":"Fried K, Krakowsky D. Probable autosomal recessive Marfan syndrome. J Med Genet 1977;14:359-61.","journal-title":"J Med Genet"}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg.21.3.173","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T05:24:06Z","timestamp":1760765046000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg.21.3.173"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1984,6]]},"references-count":20,"journal-issue":{"issue":"3","published-online":{"date-parts":[[1984,6,1]]},"published-print":{"date-parts":[[1984,6]]}},"alternative-id":["10.1136\/jmg.21.3.173"],"URL":"https:\/\/doi.org\/10.1136\/jmg.21.3.173","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"value":"0022-2593","type":"print"},{"value":"1468-6244","type":"electronic"}],"subject":[],"published":{"date-parts":[[1984,6]]}}}