{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T19:48:15Z","timestamp":1760730495658,"version":"build-2065373602"},"reference-count":37,"publisher":"BMJ","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1982,2]]},"abstract":"<jats:p>Between January 1975 and January 1980 we counselled 214 possible or obligatory carriers of haemophilia A in an attempt to provide the counsel they needed and to determine the utility of a probabilistic method of assigning the heterozygous genotype (carrier detection). We found the method of assignment to be quick and easy to use, and the single output (the final probability favouring carriership P(C)) to be understood by most counsellees. The final probabilities obtained were either very high or very low in 80% of the women, which allowed us to give clear counsel in four instances in five. The final probabilities could also be used to relate Mendelian expectation to observation within each of three subsets of women (18 mothers of sporadic haemophiliacs, 78 sisters, and 62 more distant relatives), while the aberrant likelihood ratios of 6\/36 (17%) of the obligatory carriers provided an estimate of the false negative diagnostic rate owing to lyonisation. There was no significant age effect on VIII:C or VIIIR:Ag levels of obligatory carriers, and the VIII:C levels of the obligatory carriers who had received the gene from their fathers did not differ from those of the obligatory carriers who had received the gene from their mothers. The ratios of high:low probabilities among the sisters and distant relatives of haemophiliacs conformed to genetic expectation, while the ratio among mothers of sporadic haemophiliacs suggested that their expectations of carriership were greater than 80%.<\/jats:p>\n               <jats:p>Twenty of the 214 counsellees (9%) were pregnant on the first visit, and 13 of those with low P(C)s (0\u00b70-0\u00b733) went to term and delivered 11 non-haemophilic children. Four with P(C)s between 0\u00b750 and 1\u00b700 requested amniocenteses, and one male was aborted. Three who were obligatory carriers also requested amniocentesis which led to the abortion of a second male.<\/jats:p>\n               <jats:p>Seven women who were assessed before pregnancy and found to have high P(C)s returned after becoming pregnant. All requested amniocentesis (one twice) and fetoscopy was requested for six of the seven males discovered, one male having been aborted before fetoscopy became available. Of the six males who were fetoscoped, three normal males reached term, one normal male was born prematurely, and one haemophilic male and one normal male did not survive fetoscopy.<\/jats:p>","DOI":"10.1136\/jmg.19.1.26","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T14:52:06Z","timestamp":1226328726000},"page":"26-34","source":"Crossref","is-referenced-by-count":12,"title":["Genetic counselling in haemophilia by discriminant analysis 1975-1980"],"prefix":"10.1136","volume":"19","author":[{"given":"Emily S","family":"Barrow","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Connie H","family":"Miller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Howard M","family":"Reisner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John B","family":"Graham","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1982,2,1]]},"reference":[{"issue":"32","key":"ref_1","first-page":"120","article-title":"Sex limited inheritance in Drosophila","volume":"1910","author":"Morgan, T.H.","unstructured":"Morgan TH. Sex limited inheritance in Drosophila. Science 1910;32:120-2.","journal-title":"Science"},{"issue":"32","key":"ref_2","first-page":"218","article-title":"Heredity in hemophilia","volume":"1928","author":"Macklin, M.T.","unstructured":"Macklin MT. Heredity in hemophilia. Am J Med Sci 1928;32:218-24.","journal-title":"Am J Med Sci"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1055\/s-0038-1651219","article-title":"Detection of the carrier state in hereditary coagulation disorders","volume":"19","author":"Veltkamp, J.J.; Drion, E.F.; Loeliger, E.A.","year":"1968","unstructured":"Veltkamp JJ, Drion EF, Loeliger EA. Detection of the carrier state in hereditary coagulation disorders. II. Thromb Haemostas 1968;19:403-22.","journal-title":"II. Thromb Haemostas"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1016\/S0140-6736(70)92129-X","article-title":"Immunological differentiation of three types of haemophilia and identification of some female carriers","volume":"ii:","author":"Bennett, E.; Huehns, E.R.","year":"1970","unstructured":"Bennett E, Huehns ER. Immunological differentiation of three types of haemophilia and identification of some female carriers. Lancet 1970;ii:956-8.","journal-title":"Lancet"},{"key":"ref_5","first-page":"244","article-title":"Immunologic differentiation ofclassic hemophilia (factor VIII deficiency) and von Willebrand's disease: with observations on combined deficiencies of antihemophilic factor and proaccelerin (factor V) and an acquired circulating anticoagulant against anti-hemophilic factor","volume":"50","author":"Zimmerman, T.S.; Ratnoff, O.D.; Powell, A.E.","year":"1971","unstructured":"Zimmerman TS, Ratnoff OD, Powell AE. Immunologic differentiation ofclassic hemophilia (factor VIII deficiency) and von Willebrand's disease: with observations on combined deficiencies of antihemophilic factor and proaccelerin (factor V) and an acquired circulating anticoagulant against anti-hemophilic factor. J Clin Invest 1971;50:244-54.","journal-title":"J Clin Invest"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1172\/JCI106481","article-title":"Detection of carriers of classic hemophilia using an immunologic assay for anti-hemophilic factor (factor VIII)","volume":"50","author":"Zimmerman, T.S.; Ratnoff, O.D.; Littell, A.S.","year":"1971","unstructured":"Zimmerman TS, Ratnoff OD, Littell AS. Detection of carriers of classic hemophilia using an immunologic assay for anti-hemophilic factor (factor VIII). 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Lyonization in hemophilia: a cause of error in direct detection of heterozygous carriers. Proc NY Acad Sci 1975;240:141-6.","journal-title":"Proc NY Acad Sci"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1136\/jcp.28.9.690","article-title":"Problems in the detection of carriers of haemophilia A","volume":"28","author":"Meyer, D.; Plas, A.; Allain, J.P.; Sitar, J.P.; Larrieu, M.J.","year":"1975","unstructured":"Meyer D, Plas A, Allain JP, Sitar JP, Larrieu MJ. Problems in the detection of carriers of haemophilia A. J Clin Pathol 1975;28:690-5.","journal-title":"J Clin Pathol"},{"key":"ref_14","unstructured":"Calculations of predictive odds for possible carriers of haemophilia. Thromb Haemostas 1975;34:740-7. `5 Rizza CR, Rhymes IL, Austen DEG, Kernoff PBA, Aroni SA. Detection of carriers of haemophilia: a 'blind","article-title":"Calculations of predictive odds for possible carriers of haemophilia. 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N Engl J Med 1976;294:193-8.","journal-title":"N Engl J Med"},{"key":"ref_35","first-page":"123","article-title":"The occurrence of new mutants in the X-linked recessive LeschNyhan disease","volume":"28","author":"Francke, U.; Felsenstein, J.; Gartler, S.M.","year":"1976","unstructured":"Francke U, Felsenstein J, Gartler SM, et al. The occurrence of new mutants in the X-linked recessive LeschNyhan disease. Am J Hum Genet 1976; 28:123-7.","journal-title":"Am J Hum Genet"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1016\/S0140-6736(79)92856-3","article-title":"Attitudes of haemophilia carriers to fetoscopy and amniocentesis","volume":"ii:","author":"Evans, D.I.K.; Shaw, A.","year":"1979","unstructured":"Evans DIK, Shaw A. Attitudes of haemophilia carriers to fetoscopy and amniocentesis. 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