{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:05:10Z","timestamp":1791216310062,"version":"4.1.0"},"reference-count":18,"publisher":"BMJ","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1994,12]]},"abstract":"<jats:p>Hereditary haemorrhagic telangiectasia (HHT) or Osler-Weber-Rendu syndrome is an autosomal dominant vascular dysplasia characterised by recurrent haemorrhage. Our initial linkage studies found an HHT gene to be localised to 9q3 in two large kindreds. In the present study, we examine an additional five unrelated HHT families. Linkage analysis in this region resulted in a peak multipoint location score of 13.03, 10 cM proximal of D9S60. We found significant evidence for heterogeneity of HHT. Multipoint analysis supports the family specific two point studies with odds of 3,000,000:1 showing linkage and heterogeneity over linkage and homogeneity. Four of the seven families give a posterior probability of &gt; 99% of being of the linked type, and three families appear unlinked to this region of 9q, and by multipoint analysis completely exclude the candidate region for HHT. Two new crossovers in affected persons in one of the linked families further define the proximal border of the candidate region on 9q3. A possible correlation in clinical phenotype between the 9q3 linked families and unlinked families is described. Although six of the seven families clearly meet the clinical criteria for HHT diagnosis, a significant absence of pulmonary arteriovenous malformations is seen in all three 9q3 unlinked families. Genetic heterogeneity of HHT and its potential correlation with a clinical phenotype may have a significant impact on the clinical management and treatment of HHT patients.<\/jats:p>","DOI":"10.1136\/jmg.31.12.927","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T15:23:16Z","timestamp":1226330596000},"page":"927-932","source":"Crossref","is-referenced-by-count":72,"title":["Genetic heterogeneity in hereditary haemorrhagic telangiectasia: possible correlation with clinical phenotype."],"prefix":"10.1136","volume":"31","author":[{"given":"K A","family":"McAllister","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Lennon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Bowles-Biesecker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W C","family":"McKinnon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E A","family":"Helmbold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D S","family":"Markel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C E","family":"Jackson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A E","family":"Guttmacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M A","family":"Pericak-Vance","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D A","family":"Marchuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[1994,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1002\/ana.410040207","article-title":"Neurological manifestations of hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease): report of two cases and review of the literature","volume":"4","author":"Roman, G.; Fisher, M.; Perl, D.; Poser, C.","year":"1978","unstructured":"Roman G, Fisher M, Perl D, Poser C. Neurological manifestations of hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease): report of two cases and review of the literature. Ann Neurol 1978;4:130-44.","journal-title":"Ann Neurol"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1136\/jmg.29.8.527","article-title":"Hereditary haemorrhagic telangiectasia: a clinical analysis","volume":"29","author":"Porteous, M.E.M.; Bum, J.; Proctor, S.","year":"1992","unstructured":"Porteous MEM, Bum J, Proctor S. Hereditary haemorrhagic telangiectasia: a clinical analysis. J Med Genet 1992;29: 527-30.","journal-title":"J Med Genet"},{"key":"ref_3","first-page":"363","article-title":"Clinical manifestations of hereditary hemorrhagic telangiectasia","volume":"79","author":"Reilly, P.J.; Nostrant, T.T.","year":"1984","unstructured":"Reilly PJ, Nostrant TT. Clinical manifestations of hereditary hemorrhagic telangiectasia. Am _7 Gastroenterol 1984;79: 363-7."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/0002-9343(87)90162-8","article-title":"Clinical spectrum of hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease)","volume":"82","author":"Peery, W.H.","year":"1987","unstructured":"Peery WH. Clinical spectrum of hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease). Am _7 Med 1987;82:989-96.","journal-title":"Am _7 Med"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1002\/ajmg.1320320302","article-title":"Agerelated clinical profile of hereditary hemorrhagic telangiectasia in an epidemiologically recruited population","volume":"32","author":"Plauchu, H.; Chadarevian, J.-P.; Bideau, A.; Robert, J.-M.","year":"1989","unstructured":"Plauchu H, Chadarevian J-P, Bideau A, Robert J-M. Agerelated clinical profile of hereditary hemorrhagic telangiectasia in an epidemiologically recruited population. Am JMed Genet 1989;32:291-7.","journal-title":"Am JMed Genet"},{"key":"ref_6","article-title":"Genetic linkage o(fAbhsetrreadcitta1r4y0h).emAormrh7agHiucmteGlaenngeitec(tSauspipalt)o markers","author":"McDonald, M.; Papenberg, K.; Ghosh, S.","year":"1993","unstructured":"McDonald M, Papenberg K, Ghosh S, et al. Genetic linkage o(fAbhsetrreadcitta1r4y0h).emAormrh7agHiucmteGlaenngeitec(tSauspipalt)o markers 1993;53."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/ng0294-197","article-title":"A disease locus for hereditary haemorrhagic telangiectasia maps to chromosome 9q33-34","volume":"6","author":"McDonald, M.T.; Papenberg, K.A.; Ghosh, S.","year":"1994","unstructured":"McDonald MT, Papenberg KA, Ghosh S, et al. A disease locus for hereditary haemorrhagic telangiectasia maps to chromosome 9q33-34. Nature Genet 1994;6:197-204.","journal-title":"Nature Genet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1038\/ng0294-205","article-title":"A gene for hereditary haemorrhagic telangiectasia maps to chromosome 9q3","volume":"6","author":"Shovlin, C.; Hughes, J.M.B.; Tuddenham, E.G.D.","year":"1994","unstructured":"Shovlin C, Hughes JMB, Tuddenham EGD, et al. A gene for hereditary haemorrhagic telangiectasia maps to chromosome 9q3. Nature Genet 1994;6:205-9.","journal-title":"Nature Genet"},{"key":"ref_9","first-page":"252","article-title":"Faster sequential genetic linkage computations","volume":"53","author":"Cotttingham, R.; Idury, R.; Schaffer, A.","year":"1993","unstructured":"Cotttingham R, Idury R, Schaffer A. Faster sequential genetic linkage computations. Am _7 Hum Genet 1993;53: 252-63.","journal-title":"Am _7 Hum Genet"},{"key":"ref_10","first-page":"93","article-title":"Report on the Second Intemational Workshop on Chromosome 9","volume":"64","author":"Kwiatkowski, D.J.; Amour, J.; Bale, A.","year":"1993","unstructured":"Kwiatkowski DJ, Amour J, Bale A, et al. Report on the Second Intemational Workshop on Chromosome 9. Cytogenet Cell Genet 1993;64:93-121.","journal-title":"Cytogenet Cell Genet"},{"key":"ref_11","first-page":"283","article-title":"A simple scheme for the analysis of HLA linkage in pedigrees","volume":"51","author":"Ott, K.","year":"1978","unstructured":"Ott K. A simple scheme for the analysis of HLA linkage in pedigrees. Am J7 Hum Genet 1978;51:283-90.","journal-title":"Am J7 Hum Genet"},{"key":"ref_12","article-title":"Analysis of human genetic linkage","author":"Ott, J.","year":"1991","unstructured":"Ott J. Analysis of human genetic linkage. Baltimore: Johns Hopkins University Press, 1991."},{"key":"ref_13","first-page":"769","article-title":"Epistaxis as an indication of impaired nutrition and degeneration of the vascular system","volume":"1","author":"Sutton, H.G.","year":"1864","unstructured":"Sutton HG. Epistaxis as an indication of impaired nutrition and degeneration of the vascular system. Med Mirror 1864; 1:769-72.","journal-title":"Med Mirror"},{"key":"ref_14","first-page":"362","article-title":"Hereditary epistaxis","volume":"ii:","author":"Babington, B.G.","unstructured":"Babington BG. Hereditary epistaxis. Lancet 1865;ii:362-3.","journal-title":"Lancet 1865"},{"issue":"13","key":"ref_15","first-page":"731","article-title":"Epistaxis repetees chez un sujet porteur de petits angiomies cutanes et muqueux","volume":"1896","author":"Rendu, H.","unstructured":"Rendu H. Epistaxis repetees chez un sujet porteur de petits angiomies cutanes et muqueux. Bull Soc Med Hop (Paris) 1896;13:731.","journal-title":"Bull Soc Med Hop (Paris)"},{"key":"ref_16","first-page":"333","article-title":"On a family form of recurring epistaxis with multiple telangiectases of the skin and mucous membranes. Bull3Johns Hopkins Hosp 1901; 12","author":"Osler, W.","unstructured":"Osler W. On a family form of recurring epistaxis with multiple telangiectases of the skin and mucous membranes. Bull3Johns Hopkins Hosp 1901;12:333-7."},{"key":"ref_17","first-page":"160","article-title":"Multiple hereditary developmental angiomata (telangiectases) of the skin and mucous membranes associated with recurring hemorrhages","volume":"ii:","author":"Weber, F.P.","year":"1907","unstructured":"Weber FP. Multiple hereditary developmental angiomata (telangiectases) of the skin and mucous membranes associated with recurring hemorrhages. Lancet 1907;ii: 160-","journal-title":"Lancet"},{"issue":"20","key":"ref_18","first-page":"63","article-title":"Multiple hereditary telangiectases causing hemorrhage (hereditary hemorrhagic telangiectasia)","volume":"1909","author":"Hanes, F.M.","unstructured":"Hanes FM. Multiple hereditary telangiectases causing hemorrhage (hereditary hemorrhagic telangiectasia). Bull Johns Hopkins Hosp 1909;20:63-73.","journal-title":"Bull Johns Hopkins Hosp"}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg.31.12.927","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T20:10:38Z","timestamp":1760731838000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg.31.12.927"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,12]]},"references-count":18,"journal-issue":{"issue":"12","published-online":{"date-parts":[[1994,12,1]]},"published-print":{"date-parts":[[1994,12]]}},"alternative-id":["10.1136\/jmg.31.12.927"],"URL":"https:\/\/doi.org\/10.1136\/jmg.31.12.927","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"value":"0022-2593","type":"print"},{"value":"1468-6244","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,12]]}}}