{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T04:54:05Z","timestamp":1764996845042,"version":"build-2065373602"},"reference-count":21,"publisher":"BMJ","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1998,3]]},"abstract":"<jats:p>To illustrate the variable clinical presentations and rates of progression in familial hypertrophic cardiomyopathy (FHC), phenotypes and genotypes were compared in three FHC families with different genetic defects. In the first family, the FHC abnormality was a protein truncating mutation (Gln969X) in the cardiac myosin binding protein C gene. The second family had a missense change (Asn755Lys) in the same gene. A missense mutation (Arg453Cys) in the cardiac beta myosin heavy chain gene was present in the third family. Penetrance associated with the Gln969X defect was 27% in the age range 0 to 40 years. This was considerably less than the 93% penetrance (0 to 40 years) observed in the two families with missense mutations. The variable penetrance in FHC, as well as the unpredictability of sudden cardiac death, complicates clinical diagnosis and management, including genetic counselling. Although a genetic disease with a predominantly adult onset, there are counselling issues in FHC which set it aside from other adult onset disorders.<\/jats:p>","DOI":"10.1136\/jmg.35.3.183","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T15:37:21Z","timestamp":1226331441000},"page":"183-188","source":"Crossref","is-referenced-by-count":18,"title":["Counselling issues in familial hypertrophic cardiomyopathy."],"prefix":"10.1136","volume":"35","author":[{"given":"B","family":"Yu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J A","family":"French","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R W","family":"Jeremy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P","family":"French","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D R","family":"McTaggart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M R","family":"Nicholson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C","family":"Semsarian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D R","family":"Richmond","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R J","family":"Trent","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1998,3,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1136\/adc.59.10.971","article-title":"Hypertrophic cardiomyopathy: an important cause of sudden death","volume":"59","author":"McKenna, W.J.; Deanfield, J.E.","year":"1984","unstructured":"McKenna WJ, Deanfield JE. 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Circulation 1995;91: 532-40.","journal-title":"Circulation"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1056\/NEJM199703133361107","article-title":"The management of hypertrophic cardiomyopathy","volume":"336","author":"Spirito, P.; Seidman, C.E.; McKenna, W.J.; Maron, B.J.","year":"1997","unstructured":"Spirito P, Seidman CE, McKenna WJ, Maron BJ. The management of hypertrophic cardiomyopathy. N Engl Jf Med 1997;336:775-85.","journal-title":"N Engl Jf Med"},{"key":"ref_5","first-page":"348","article-title":"Equivocal and borderline myocardial hypertrophy in relatives of patients with hypertrophic cardiomyopathy: possible implications","volume-title":"genetics of the disease. Cardiology 1988","volume":"75","author":"Autore, C.; Fragola, P.V.; Picelli, A.","unstructured":"Autore C, Fragola PV, Picelli A, et al. Equivocal and borderline myocardial hypertrophy in relatives of patients with hypertrophic cardiomyopathy: possible implications in genetics of the disease. Cardiology 1988;75:348-56."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1056\/NEJM199504203321603","article-title":"Mutations in the genes for cardiac troponin T and a-tropomyosin in hypertrophic cardiomyopathy","volume":"332","author":"Watkins, H.; McKenna, W.I.; Thierfelder, L.","year":"1995","unstructured":"Watkins H, McKenna WI, Thierfelder L, et al. Mutations in the genes for cardiac troponin T and a-tropomyosin in hypertrophic cardiomyopathy. N Engl Med 1995;332: 1058-64.","journal-title":"N Engl Med"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1172\/JCI116957","article-title":"Prognostic implications of novel beta cardiac myosin heavy chain gene mutations that cause familial hypertrophic cardiomyopathy","volume":"93","author":"Anan, R.; Greve, G.; Thierfelder, L.","year":"1994","unstructured":"Anan R, Greve G, Thierfelder L, et al. Prognostic implications of novel beta cardiac myosin heavy chain gene mutations that cause familial hypertrophic cardiomyopathy. Clin Invest 1994;93:280-5.","journal-title":"Clin Invest"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1136\/jmg.35.3.205","article-title":"Molecular pathology of familial hypertrophic cardiomyopathy caused by mutations in the cardiac myosin binding protein C gene","volume":"35","author":"Yu, B.; French, J.A.; Carrier, L.","year":"1998","unstructured":"Yu B, French JA, Carrier L, et al. Molecular pathology of familial hypertrophic cardiomyopathy caused by mutations in the cardiac myosin binding protein C gene. J7 Med Genet 1998;35:205-10.","journal-title":"J7 Med Genet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/ng0596-63","article-title":"Mutations in either the essential or regulatory light chains of myosin are associated with a rare myopathy in human heart and skeletal muscle","volume":"13","author":"Poetter, K.; Jiang, H.; Hassanzadeh, S.","year":"1996","unstructured":"Poetter K, Jiang H, Hassanzadeh S, et al. Mutations in either the essential or regulatory light chains of myosin are associated with a rare myopathy in human heart and skeletal muscle. Nat Genet 1996;13:63-9.","journal-title":"Nat Genet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/ng0897-379","article-title":"Mutations in the cardiac troponin I gene associated with hypertrophic cardiomyopathy","volume":"16","author":"Kimura, A.; Harada, H.; Park, J.E.","year":"1997","unstructured":"Kimura A, Harada H, Park JE, et al. Mutations in the cardiac troponin I gene associated with hypertrophic cardiomyopathy. Nat Genet 1997;16:379-82.","journal-title":"Nat Genet"},{"key":"ref_11","first-page":"1216","article-title":"Familial hypertrophic cardiomyopathy with Wolff-Parkinson-White syndrome maps to a locus on chromosome 7q3","volume":"96","author":"MacRae, C.A.; Ghaisas, N.; Kass, S.","year":"1995","unstructured":"MacRae CA, Ghaisas N, Kass S, et al. 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Circulation 1994; 89:22-32.","journal-title":"Circulation"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1136\/hrt.63.5.308","article-title":"Sudden death in hypertrophic cardiomyopathy with normal left ventricular mass","volume":"63","author":"Maron, B.J.; Kragel, A.H.; Roberts, W.C.","year":"1990","unstructured":"Maron BJ, Kragel AH, Roberts WC. Sudden death in hypertrophic cardiomyopathy with normal left ventricular mass. Br HeartJ 1990;63:308-10.","journal-title":"Br HeartJ"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1111\/j.1365-2559.1995.tb00267.x","article-title":"Hypertrophic cardiomyopathy pathology and pathogenesis","volume":"26","author":"Davis, M.J.; McKenna, W.J.","year":"1995","unstructured":"Davis MJ, McKenna WJ. Hypertrophic cardiomyopathy pathology and pathogenesis. Histopathology 1995;26:493-500.","journal-title":"Histopathology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1016\/0140-6736(90)92713-R","article-title":"Should we test children for \"adult\" genetic diseases?","volume":"335","author":"Harper, P.S.; Clarke, A.","year":"1990","unstructured":"Harper PS, Clarke A. Should we test children for \"adult\" genetic diseases? Lancet 1990;335: 1205-6.","journal-title":"Lancet"},{"key":"ref_20","first-page":"785","article-title":"The genetic testing of children","volume":"31","author":"Clarke, A.","year":"1994","unstructured":"Clarke A. The genetic testing of children. Jf Med Genet 1994;31:785-97.","journal-title":"Jf Med Genet"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1136\/bmj.310.6983.856","article-title":"Genetic testing for familial hypertrophic cardiomyopathy in newborn infants","volume":"310","author":"Ryan, M.P.; French, J.; al-Mahdawi, S.","year":"1995","unstructured":"Ryan MP, French J, al-Mahdawi S, et al. Genetic testing for familial hypertrophic cardiomyopathy in newborn infants. 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