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Clinical Expression in Patients With Hypertrophic Cardiomyopathy Caused by Cardiac Myosin-Binding Protein C Gene Mutation

1999; Lippincott Williams & Wilkins; Volume: 100; Issue: 4 Linguagem: Inglês

10.1161/circ.100.4.446/-c

1524-4539

Yoshinori L. Doi, Hiroaki Kitaoka, Nobuhiko Hitomi, Manatsu Satoh, Akinori Kimura,

Williams Syndrome Research

HomeCirculationVol. 100, No. 4Clinical Expression in Patients With Hypertrophic Cardiomyopathy Caused by Cardiac Myosin-Binding Protein C Gene Mutation Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBClinical Expression in Patients With Hypertrophic Cardiomyopathy Caused by Cardiac Myosin-Binding Protein C Gene Mutation Yoshinori L. Doi, Hiroaki Kitaoka and Nobuhiko Hitomi Manatsu Satoh and Akinori Kimura Yoshinori L. DoiYoshinori L. Doi Department of Medicine and Geriatrics, Kochi Medical School, Kochi, Japan , Hiroaki KitaokaHiroaki Kitaoka Department of Medicine and Geriatrics, Kochi Medical School, Kochi, Japan and Nobuhiko HitomiNobuhiko Hitomi Department of Medicine and Geriatrics, Kochi Medical School, Kochi, Japan Manatsu SatohManatsu Satoh Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan and Akinori KimuraAkinori Kimura Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan Originally published21 Mar 2018https://doi.org/10.1161/circ.100.4.446/-cCirculation. 1999;100:446–449To the Editor:Hypertrophic cardiomyopathy is a primary cardiac disorder, mostly genetically transmitted, with a heterogeneous clinical and morphological expression. Analysis of the clinical expression of several genetic alterations has previously focused mainly on unfavorable manifestations. In this regard, recent articles by Charron and colleagues1 and by Niimura and colleagues2 that describe delayed expression of cardiac hypertrophy and a favorable clinical course in patients with mutations in the gene for cardiac myosin-binding protein C (MyBP-C) are indeed important contributions to an understanding of phenotype-genotype correlations at the mild end of the spectrum of the disease. However, these reports did not include precise morphological distribution of left ventricular hypertrophy, which is of clinical importance in the diagnosis and management of patients with this disorder.We had opportunities to study 6 probands from 6 small Japanese families living in Kochi prefecture who were found to have the same mutation in the cardiac MyBP-C gene: a 1-base deletion at codon 593 from TCC (Ser) to CC in exon 18.3 Of 30 adult family members screened, 14 were identified as having this MyBP-C mutation. Although disease penetrance was incomplete, 90% of all patients and 80% of those under the age of 50 years had cardiac hypertrophy. The mean maximal wall thickness was 21±3 mm. Most patients revealed hypertrophy of both the ventricular septum and the free wall: 14 with Maron type III, 1 with type I, 1 with type IV, and 2 with diffuse concentric hypertrophy. There was no patient with apical hypertrophy, which was characteristically reported among Japanese patients.4 It would be interesting and clinically valuable to know what kind of morphological patterns of left ventricular hypertrophy, assessed by 2-dimensional echocardiography, have been seen in the patients reported by Charron and colleagues.Concerning the natural history, sudden cardiac death was not observed during a follow-up period of 54.5±57.1 months (range, 1 to 160 months) in our patients, and 3 patients reached the age of >70 years. However, it is worth noting that 4 patients gradually progressed to the stage of left ventricular dilation and dysfunction later in their lives, a fact that has not been reported previously.This phenotype-genotype information will be of significant importance for the practicing clinician, because left ventricular hypertrophy, as well as left ventricular dilation and dysfunction, often occurs in elderly patients, particularly in association with systolic hypertension. References 1 Charron P, Dubourg O, Desnos M, Bennaceur M, Carrier L, Camproux A-C, Isnard R, Hagege A, Langlard JM, Bonne G, Richard P, Hainque B, Bouhour J-B, Schwartz K, Komajda M. Clinical features and prognostic implications of familial hypertrophic cardiomyopathy related to the cardiac myosin-binding protein C gene. Circulation.1998; 97:2230–2236.CrossrefMedlineGoogle Scholar2 Niimura H, Bachinski LL, Sangwatanaroj S, Watkins H, Chudley AE, McKenna W, Kristinsson A, Roberts R, Sole M, Maron BJ, Seidman JG, Seidman CE. Mutations in the gene for cardiac myosin-binding protein C and late-onset familial hypertrophic cardiomyopathy. N Engl J Med.1998; 338:1248–1257.CrossrefMedlineGoogle Scholar3 Kimura A, Harada H, Park J-E, Nishi H, Satoh M, Takahashi M, Hiroi S, Sasaoka T, Ohbuchi N, Nakamura T, Koyanagi T, Hwang T-H, Choo J-A, Chung K-S, Hasegawa A, Nagai R, Okazaki O, Nakamura H, Matsuzaki M, Sakamoto T, Toshima H, Koga Y, Imaizumi T, Sasazuki T. Mutations in the cardiac troponin I gene associated with hypertrophic cardiomyopathy. Nat Genet.1997; 16:379–382.CrossrefMedlineGoogle Scholar4 Koga Y, Katoh A, Matsuyama K, Ikeda H, Hiyamuta K, Toshima H, Imaizumi T. Disappearance of giant negative T waves in patients with the Japanese form of apical hypertrophy. J Am Coll Cardiol.1995; 26:1672–1678.CrossrefMedlineGoogle ScholarcirculationahaCirculationCirculationCirculation0009-73221524-4539Lippincott Williams & WilkinsResponseCharron Philippe, MD, Bennaceur Mohammed, MD, Isnard Richard, MD, Komajda Michel, MD, Carrier Lucie, PhD, Bonne Gisele, PhD, Schwartz Ketty, PhD, Camproux Anne-Claude, PhD, Richard Pascale, PhD, Hainque Bernard, PhD, Dubourg Olivier, MD, Desnos Michel, MD, Hagege Albert, MD, Langlard Jean Marc, MD, and Bouhour Jean-Brieuc, MD27071999We thank Dr Doi et al for their comments about our articleR1 on phenotype-genotype analysis related to the cardiac myosin binding protein C (MyBP-C) gene in familial hypertrophic cardiomyopathy (FHC). They screened Japanese families, found a mutation in the MyBP-C gene in 6 of them (14 adult members), and analyzed some of their clinical features.They found that penetrance of the disease was incomplete, as in our experience, but was as high as 80% before 50 years of age. First, the penetrance of the disease depends heavily on the diagnostic criteria used, as was recently shown in children.R2 Therefore, it would be interesting to know the diagnostic criteria used by Doi et al. Second, in addition to the causative mutation or gene, many factors could modulate the expression of the disease and could explain the difference observed between the Japanese and French populations. These factors include mean age, sex ratio, modifier gene (such as the ACE I/D polymorphism),R3 and unknown environmental factors.Interestingly, a mean follow-up of 54 months was available in families studied by Doi et al, and no sudden cardiac death was observed. This confirms the good prognosis observed in our study in young subjects.R1 The fact that 4 patients progressed to left ventricular dilation and dysfunction is also in accordance with our findings, because we observed 4 cardiac deaths or transplantations related to congestive heart failure (mean age, 65±9 years) in our population. This evolution appears not specific of families with a mutation in the MyBP-C gene, because it was described in families with a mutation in the β-myosin heavy chain gene.R1Finally, the distribution of left ventricular hypertrophy (LVH) was not described in our study (it was not our purpose, because the distribution of LVH appears to be of little interest for prognostic implications). However, in 46 subjects with LVH, of the 76 carriers of a mutation in the MyBP-C gene, we found 2 (4.3%) subjects with Maron type I hypertrophy, 19 (41.3%) with type II, 24 (52.2%) with type III, and 1 with type IV (2.2%). As previously shown in FHC related to other genes,R4 the morphological distribution of LVH was therefore variable in families related to the MyBP-C gene, even within a given family. Previous Back to top Next FiguresReferencesRelatedDetailsCited By Biagini E, Coccolo F, Ferlito M, Perugini E, Rocchi G, Bacchi-Reggiani L, Lofiego C, Boriani G, Prandstraller D, Picchio F, Branzi A and Rapezzi C (2005) Dilated-Hypokinetic Evolution of Hypertrophic Cardiomyopathy, Journal of the American College of Cardiology, 10.1016/j.jacc.2005.04.062, 46:8, (1543-1550), Online publication date: 1-Oct-2005. Kubo T, Kitaoka H, Okawa M, Matsumura Y, Hitomi N, Yamasaki N, Furuno T, Takata J, Nishinaga M, Kimura A and Doi Y (2005) Lifelong Left Ventricular Remodeling of Hypertrophic Cardiomyopathy Caused by a Founder Frameshift Deletion Mutation in the Cardiac Myosin-Binding Protein C Gene Among Japanese, Journal of the American College of Cardiology, 10.1016/j.jacc.2005.05.087, 46:9, (1737-1743), Online publication date: 1-Nov-2005. Konno T, Shimizu M, Ino H, Matsuyama T, Yamaguchi M, Terai H, Hayashi K, Mabuchi T, Kiyama M, Sakata K, Hayashi T, Inoue M, Kaneda T and Mabuchi H (2003) A novel missense mutation in the myosin binding protein-C gene is responsible for hypertrophic cardiomyopathy with left ventricular dysfunction and dilation in elderly patients, Journal of the American College of Cardiology, 10.1016/S0735-1097(02)02957-1, 41:5, (781-786), Online publication date: 1-Mar-2003. July 27, 1999Vol 100, Issue 4 Advertisement Article InformationMetrics Copyright © 1999 by American Heart Associationhttps://doi.org/10.1161/circ.100.4.446/-c Originally publishedMarch 21, 2018 PDF download Advertisement