Case report
Complex phenotype linked to a mutation in exon 11 of the lamin A/C gene: Hypertrophic cardiomyopathy, atrioventricular block, severe dyslipidemia and diabetes
Fenótipo complexo associado a uma mutação no exão 11 do gene da lâmina A/C: miocardiopatia hipertrófica, bloqueio auriculoventricular, dislipidemia grave e diabetes mellitus
Ana Rita G. Francisco
, Inês Santos Gonçalves, Fátima Veiga, Mónica Mendes Pedro, Fausto J. Pinto, Dulce Brito
Autor para correspondência
Cardiology Department, Santa Maria University Hospital, CHLN, CAML, CCUL, Faculty of Medicine, University of Lisbon, Lisbon, Portugal
Lido
4985
Vezesque se leu este artigo
1879
Total PDF
3106
Total HTML
Compartilhar estatísticas
array:25 [ "pii" => "S0870255117305590" "issn" => "08702551" "doi" => "10.1016/j.repc.2016.07.018" "estado" => "S300" "fechaPublicacion" => "2017-09-01" "aid" => "1047" "copyright" => "Sociedade Portuguesa de Cardiologia" "copyrightAnyo" => "2017" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "crp" "cita" => "Rev Port Cardiol. 2017;36:669.e1-4" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 1999 "formatos" => array:3 [ "EPUB" => 172 "HTML" => 1363 "PDF" => 464 ] ] "Traduccion" => array:1 [ "en" => array:20 [ "pii" => "S2174204917302441" "issn" => "21742049" "doi" => "10.1016/j.repce.2017.09.002" "estado" => "S300" "fechaPublicacion" => "2017-09-01" "aid" => "1047" "copyright" => "Sociedade Portuguesa de Cardiologia" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "crp" "cita" => "Rev Port Cardiol. 2017;36:669.e1-4" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 1642 "formatos" => array:3 [ "EPUB" => 182 "HTML" => 1114 "PDF" => 346 ] ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Case report</span>" "titulo" => "Complex phenotype linked to a mutation in exon 11 of the lamin A/C gene: Hypertrophic cardiomyopathy, atrioventricular block, severe dyslipidemia and diabetes" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "pt" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "669.e1" "paginaFinal" => "669.e4" ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Fenótipo complexo associado a uma mutação no exão 11 do gene da lâmina A/C: miocardiopatia hipertrófica, bloqueio auriculoventricular, dislipidemia grave e diabetes <span class="elsevierStyleItalic">mellitus</span>" ] ] "contieneResumen" => array:2 [ "en" => true "pt" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Ana Rita G. Francisco, Inês Santos Gonçalves, Fátima Veiga, Mónica Mendes Pedro, Fausto J. Pinto, Dulce Brito" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Ana Rita G." "apellidos" => "Francisco" ] 1 => array:2 [ "nombre" => "Inês" "apellidos" => "Santos Gonçalves" ] 2 => array:2 [ "nombre" => "Fátima" "apellidos" => "Veiga" ] 3 => array:2 [ "nombre" => "Mónica" "apellidos" => "Mendes Pedro" ] 4 => array:2 [ "nombre" => "Fausto J." "apellidos" => "Pinto" ] 5 => array:2 [ "nombre" => "Dulce" "apellidos" => "Brito" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S0870255117305590" "doi" => "10.1016/j.repc.2016.07.018" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255117305590?idApp=UINPBA00004E" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2174204917302441?idApp=UINPBA00004E" "url" => "/21742049/0000003600000009/v1_201709220127/S2174204917302441/v1_201709220127/en/main.assets" ] ] "itemSiguiente" => array:20 [ "pii" => "S0870255117305607" "issn" => "08702551" "doi" => "10.1016/j.repc.2016.08.014" "estado" => "S300" "fechaPublicacion" => "2017-09-01" "aid" => "1048" "copyright" => "Sociedade Portuguesa de Cardiologia" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "crp" "cita" => "Rev Port Cardiol. 2017;36:671.e1-4" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 2114 "formatos" => array:3 [ "EPUB" => 165 "HTML" => 1557 "PDF" => 392 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Case report</span>" "titulo" => "Missing grafts and the potential for inappropriate revascularization" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "pt" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "671.e1" "paginaFinal" => "671.e4" ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Falta de enxertos e o potencial de uma revascularização inapropriada" ] ] "contieneResumen" => array:2 [ "en" => true "pt" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2762 "Ancho" => 3000 "Tamanyo" => 463688 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">(A) Case B showing an aortogram with no grafts visualized; (B) case B showing widely patent saphenous vein graft; (C) case C showing occluded SVG graft; (D) case C showing SVG graft after successful intervention. SVG: saphenous vein graft.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Oluwaseyi Bolorunduro, Mohamed Morsy, Yaser Cheema, Rami N. Khouzam" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Oluwaseyi" "apellidos" => "Bolorunduro" ] 1 => array:2 [ "nombre" => "Mohamed" "apellidos" => "Morsy" ] 2 => array:2 [ "nombre" => "Yaser" "apellidos" => "Cheema" ] 3 => array:2 [ "nombre" => "Rami N." "apellidos" => "Khouzam" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2174204917302453" "doi" => "10.1016/j.repce.2016.08.011" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2174204917302453?idApp=UINPBA00004E" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255117305607?idApp=UINPBA00004E" "url" => "/08702551/0000003600000009/v1_201709150927/S0870255117305607/v1_201709150927/en/main.assets" ] "itemAnterior" => array:20 [ "pii" => "S0870255116303377" "issn" => "08702551" "doi" => "10.1016/j.repc.2016.11.013" "estado" => "S300" "fechaPublicacion" => "2017-09-01" "aid" => "1038" "copyright" => "Sociedade Portuguesa de Cardiologia" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "rev" "cita" => "Rev Port Cardiol. 2017;36:655-68" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 27948 "formatos" => array:3 [ "EPUB" => 228 "HTML" => 25432 "PDF" => 2288 ] ] "pt" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Artigo de Revisão</span>" "titulo" => "Sacubitril/valsartan: um importante avanço no <span class="elsevierStyleItalic">puzzle</span> terapêutico da insuficiência cardíaca" "tienePdf" => "pt" "tieneTextoCompleto" => "pt" "tieneResumen" => array:2 [ 0 => "pt" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "655" "paginaFinal" => "668" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Sacubitril/valsartan: An important piece in the therapeutic puzzle of heart failure" ] ] "contieneResumen" => array:2 [ "pt" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "pt" => true ] "contienePdf" => array:1 [ "pt" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figura 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1919 "Ancho" => 3160 "Tamanyo" => 342457 ] ] "descripcion" => array:1 [ "pt" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Mecanismo de ação farmacológica do LCZ696 (adaptado de Vardeny et al.<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">2</span></a>).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Pedro Marques da Silva, Carlos Aguiar" "autores" => array:2 [ 0 => array:2 [ "nombre" => "Pedro" "apellidos" => "Marques da Silva" ] 1 => array:2 [ "nombre" => "Carlos" "apellidos" => "Aguiar" ] ] ] ] ] "idiomaDefecto" => "pt" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2174204917302374" "doi" => "10.1016/j.repce.2016.11.017" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2174204917302374?idApp=UINPBA00004E" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255116303377?idApp=UINPBA00004E" "url" => "/08702551/0000003600000009/v1_201709150927/S0870255116303377/v1_201709150927/pt/main.assets" ] "en" => array:18 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Case report</span>" "titulo" => "Complex phenotype linked to a mutation in exon 11 of the lamin A/C gene: Hypertrophic cardiomyopathy, atrioventricular block, severe dyslipidemia and diabetes" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "669.e1" "paginaFinal" => "669.e4" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Ana Rita G. Francisco, Inês Santos Gonçalves, Fátima Veiga, Mónica Mendes Pedro, Fausto J. Pinto, Dulce Brito" "autores" => array:6 [ 0 => array:4 [ "nombre" => "Ana Rita G." "apellidos" => "Francisco" "email" => array:1 [ 0 => "ana.r.francisco@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "Inês" "apellidos" => "Santos Gonçalves" ] 2 => array:2 [ "nombre" => "Fátima" "apellidos" => "Veiga" ] 3 => array:2 [ "nombre" => "Mónica" "apellidos" => "Mendes Pedro" ] 4 => array:2 [ "nombre" => "Fausto J." "apellidos" => "Pinto" ] 5 => array:2 [ "nombre" => "Dulce" "apellidos" => "Brito" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Cardiology Department, Santa Maria University Hospital, CHLN, CAML, CCUL, Faculty of Medicine, University of Lisbon, Lisbon, Portugal" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Fenótipo complexo associado a uma mutação no exão 11 do gene da lâmina A/C: miocardiopatia hipertrófica, bloqueio auriculoventricular, dislipidemia grave e diabetes <span class="elsevierStyleItalic">mellitus</span>" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The lamin A/C (<span class="elsevierStyleItalic">LMNA</span>) gene is mapped to the long arm of chromosome 1 (1q21-23) and contains 12 exons.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">1</span></a> This gene encodes lamins A and C, nuclear envelope proteins with an important role in nuclear cohesion and chromatin organization. They are critical to the performance of the peripheral nervous system, skeletal muscle, osteoblastogenesis and bone formation, and are also involved in the prevention of muscle fat infiltration.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Mutations in the <span class="elsevierStyleItalic">LMNA</span> gene are linked to several diseases, called laminopathies, which display heterogeneous phenotypes, including Emery-Dreifuss muscular dystrophy, limb-girdle muscular dystrophy, Dunnigan-type familial partial lipodystrophy (FPLD type 2), Charcot-Marie-Tooth disease, mandibuloacral dysplasia, Hutchinson-Gilford progeria syndrome, atypical forms of Werner syndrome and restrictive dermopathy.<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">2–5</span></a> Regarding cardiovascular disease, the phenotype is typically dilated cardiomyopathy with conduction defects (atrial arrhythmia or atrioventricular [AV] block), progression to heart failure and a high incidence of sudden cardiac death.<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">3,6–8</span></a> There is only one case report of hypertrophic cardiomyopathy associated with mutations in this gene,<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">3</span></a> and other rare associations with ventricular hypertrophy,<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">3,4,9</span></a> left ventricular noncompaction and arrhythmogenic right ventricular dysplasia have been described.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">10</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Disorders caused by <span class="elsevierStyleItalic">LMNA</span> mutations, like FPLD type 2, are also linked to metabolic abnormalities characterized by abnormal fat distribution, insulin resistance, diabetes, dyslipidemia, high blood pressure, hepatic steatosis and increased risk for coronary heart disease.<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">4,5,9,11</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The lipodystrophic and myopathic phenotypes are thought to be mutually exclusive, but in rare cases heterozygous <span class="elsevierStyleItalic">LMNA</span> mutations are associated with cardiac and skeletal muscular involvement.<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">9,12–14</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">In this report we describe a new phenotype linked to a mutation in exon 11 of the <span class="elsevierStyleItalic">LMNA</span> gene: hypertrophic cardiomyopathy, AV block, severe dyslipidemia and diabetes.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Case report</span><p id="par0030" class="elsevierStylePara elsevierViewall">The authors present the case of a 64-year-old woman with metabolic syndrome – obesity (body mass index 30 kg/m<span class="elsevierStyleSup">2</span>), severe dyslipidemia (fasting serum triglycerides [TG] 960 mg/dl, total cholesterol [TC] 273 mg/dl, high-density lipoprotein cholesterol 40 mg/dl) and diabetes (HbA1c 6.8%) – who presented in January 2013 with fatigue on minimal exertion in NYHA functional class II. On cardiac auscultation, a systolic murmur was audible along the upper left sternal border, increasing with the Valsalva maneuver. The electrocardiogram (ECG) revealed sinus rhythm with normal interventricular conduction. Transthoracic echocardiography (echo) identified severe left ventricular hypertrophy (LVH), with basal septal wall 21.7 mm and posterior wall 11.8 mm, systolic anterior motion of the mitral valve and a dynamic left ventricular outflow gradient of 111 mmHg at rest. There was no family history of cardiac disease. Genetic screening, testing a panel of 51 genes associated with cardiomyopathies by oligonucleotide-based target capture followed by next-generation sequencing, identified a point mutation in exon 11 of the <span class="elsevierStyleItalic">LMNA</span> gene (c.1718C>T, p.Ser573Leu). Besides obesity, diabetes and severe dyslipidemia, no other phenotypic characteristics related to the <span class="elsevierStyleItalic">LMNA</span> mutation were identified.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Despite medical treatment with bisoprolol and amlodipine, the patient's heart failure symptoms worsened and septal alcohol ablation was performed. A satisfactory final result was achieved with symptomatic improvement and gradient reduction (maximum subaortic gradient of 25 mmHg at rest and 37 mmHg after the Valsalva maneuver, with septal basal wall of 14.2 mm, measured six days after the procedure).</p><p id="par0040" class="elsevierStylePara elsevierViewall">Several months later, despite optimized medication, heart failure symptoms worsened, with progression of LVH (basal septal wall 18.3 mm) and recurrence of outflow obstruction (124 mmHg at rest). Morrow myectomy was performed with a good final result (maximum subaortic gradient of 10 mmHg after Valsalva maneuver). After surgery the ECG revealed sinus rhythm and a left bundle branch block pattern, with QRS duration of 160 ms. The patient remained clinically stable under treatment with bisoprolol, amlodipine, spironolactone, furosemide, rosuvastatin and metformin. Three months later she presented at the emergency department with seizure and worsening fatigue. A pattern of complete AV block at 30 bpm was detected and a temporary transvenous cardiac pacemaker was implanted. After 48 hours of bisoprolol washout, the AV block pattern persisted and the patient remained pacemaker-dependent. Echo evaluation showed mild LVH (septal wall 12.1 mm and posterior wall 12.8 mm), no left ventricular outflow tract obstruction, paradoxical septal motion and left ventricular ejection fraction of 45%. Considering her history of heart failure, the reduction in ejection fraction and the broad QRS complex, a cardiac resynchronization device was implanted.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Regarding the metabolic disorder, laboratory tests on admission revealed a fasting serum TG level of 3260 mg/dl and TC of 640 mg/dl. Although there were no acute complications related to severe dyslipidemia, in order to achieve rapid and effective lowering of TG values and to prevent complications due to hypertriglyceridemia, particularly acute pancreatitis, therapeutic plasma exchange was performed. Treatment with lipid-lowering agents was also intensified, with up-titration of rosuvastatin and addition of bezafibrate and ezetimibe, and beta-blocker therapy was reintroduced. The patient was discharged, and at the first reassessment one month later she was asymptomatic, with 100% pacing capture and a significantly improved lipid profile. At six-month follow-up she remained in NYHA functional class I.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0050" class="elsevierStylePara elsevierViewall">Mutations in the <span class="elsevierStyleItalic">LMNA</span> gene are associated with a highly heterogeneous group of phenotypes. The molecular mechanisms through which lamin A/C mutations lead to such phenotypic variability are poorly understood. Several hypotheses have been advocated, including mechanical shearing, differential gene regulation by interaction with nuclear chromatin, and interaction between mutant lamins and other nuclear proteins.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">15</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Of the 12 exons composing the human <span class="elsevierStyleItalic">LMNA</span> gene, exons 11 and 12 are specific for lamin A, while mutations in the other exons (1-10) affect both variants (lamin A and C).<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">3</span></a> Usually, mutations affecting both splice forms result in more severe phenotypes, and, mutations in exon 11 – affecting only the globular domain specific to the lamin A isoform – are associated with milder phenotypes regarding lipodystrophy and myopathy, as was the case with this patient.<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">3,13</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Cardiac involvement with lipodystrophy has been previously associated with <span class="elsevierStyleItalic">LMNA</span> mutations, but the cardiac phenotype is usually dilated cardiomyopathy associated with conduction defects. In contrast, our patient had a pattern of hypertrophic cardiomyopathy, and conduction disturbances requiring pacemaker implantation. Her systolic dysfunction (as demonstrated by left ventricular ejection fraction of 45%), broad QRS, and history of heart failure prompted the implantation of a cardiac resynchronization device.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">15</span></a> For patients with AV block and systolic dysfunction, biventricular pacing not only reduces the risk of mortality and morbidity, but also leads to better clinical outcomes, compared with right ventricular pacing.<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">16</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">The <span class="elsevierStyleItalic">LMNA</span> mutation identified in our patient (c.1718C>T, Ser573Leu) was first documented in 2003 by Taylor et al.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">17</span></a> This mutation had been identified in heterozygosity in a patient with dilated cardiomyopathy and conduction defects<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">17</span></a> and in homozygosity in a patient with arthropathy, tendinous calcinosis, and progeroid features without any type of cardiomyopathy.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">18</span></a> Because heterozygosity for this mutation can cause cardiomyopathy without lipodystrophy or lipodystrophy without cardiomyopathy, Lanktree et al. suggested that additional factors, genetic or environmental, may contribute to the precise tissue involvement.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">19</span></a> This specific mutation has not previously been associated with hypertrophic cardiomyopathy. However, the significant LVH (septal thickness 21 mm) in the absence of other identifiable cause, and the identification of a single pathogenic mutation in a sarcomere-related gene (point mutation in exon 11 in the <span class="elsevierStyleItalic">LMNA</span> gene, in a panel of 51 genes associated with cardiomyopathies), suggested a causal association between the molecular genetic findings and the cardiac phenotype in this patient.</p><p id="par0070" class="elsevierStylePara elsevierViewall">In conclusion, the association between <span class="elsevierStyleItalic">LMNA</span> gene mutations and different phenotypes is complex and not fully understood, and can present with a broad spectrum of severity. Of note, the occurrence and severity of myopathic and lipoatrophic phenotypes are not related and the correlation of newly identified mutations and individual clinical phenotypes is mandatory. We report a new and complex phenotype linked to a mutation in exon 11 in the <span class="elsevierStyleItalic">LMNA</span> gene (c.1718C>T, p.Ser573Leu) associated with hypertrophic cardiomyopathy, atrioventricular block, severe dyslipidemia and diabetes.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Ethical disclosures</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Protection of human and animal subjects</span><p id="par0075" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Confidentiality of data</span><p id="par0080" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols of their work center on the publication of patient data.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Right to privacy and informed consent</span><p id="par0085" class="elsevierStylePara elsevierViewall">The authors have obtained the written informed consent of the patients or subjects mentioned in the article. The corresponding author is in possession of this document.</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Author contributions</span><p id="par0095" class="elsevierStylePara elsevierViewall">ARF and DB were responsible for the conception, design and drafting of the article. All the authors made substantial contributions to the article, through data acquisition, data interpretation and revision. All authors gave their final approval of the version to be submitted.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conflicts of interest</span><p id="par0090" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres901293" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec882331" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres901294" "titulo" => "Resumo" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec882330" "titulo" => "Palavras-chave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Case report" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Discussion" ] 7 => array:3 [ "identificador" => "sec0020" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0035" "titulo" => "Right to privacy and informed consent" ] ] ] 8 => array:2 [ "identificador" => "sec0045" "titulo" => "Author contributions" ] 9 => array:2 [ "identificador" => "sec0040" "titulo" => "Conflicts of interest" ] 10 => array:2 [ "identificador" => "xack299798" "titulo" => "Acknowledgments" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-04-15" "fechaAceptado" => "2016-07-13" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec882331" "palabras" => array:6 [ 0 => "Hypertrophic cardiomyopathy" 1 => "Lamin A/C" 2 => "LMNA gene" 3 => "Dyslipidemia" 4 => "Diabetes" 5 => "Atrioventricular block" ] ] ] "pt" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palavras-chave" "identificador" => "xpalclavsec882330" "palabras" => array:6 [ 0 => "Miocardiopatia hipertrófica" 1 => "Lâmina A/C" 2 => "Gene LMNA" 3 => "Dislipidemia" 4 => "Diabetes" 5 => "Bloqueio auriculoventricular" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The lamin A/C (<span class="elsevierStyleItalic">LMNA</span>) gene encodes lamins A and C, which have an important role in nuclear cohesion and chromatin organization. Mutations in this gene usually lead to the so-called laminopathies, the primary cardiac manifestations of which are dilated cardiomyopathy and intracardiac conduction defects. Some mutations, associated with lipodystrophy but not cardiomyopathy, have been linked to metabolic abnormalities such as diabetes and severe dyslipidemia. Herein we describe a new phenotype associated with a mutation in exon 11 of the <span class="elsevierStyleItalic">LMNA</span> gene: hypertrophic cardiomyopathy, atrioventricular block, severe dyslipidemia and diabetes.</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A 64-year-old woman with hypertrophic cardiomyopathy and a point mutation in exon 11 of the <span class="elsevierStyleItalic">LMNA</span> gene (c.1718C>T, Ser573Leu) presented with severe symptomatic ventricular hypertrophy and left ventricular outflow tract obstruction. She underwent septal alcohol ablation, followed by Morrow myectomy. The patient was also diagnosed with severe dyslipidemia, diabetes and obesity, and fulfilled diagnostic criteria for metabolic syndrome. No other characteristics of <span class="elsevierStyleItalic">LMNA</span> mutation-related phenotypes were identified. The development of type III atrioventricular block with no apparent cause, and mildly depressed systolic function, prompted referral for cardiac resynchronization therapy.</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">In conclusion, the association between <span class="elsevierStyleItalic">LMNA</span> mutations and different phenotypes is complex and not fully understood, and can present with a broad spectrum of severity.</p></span>" ] "pt" => array:2 [ "titulo" => "Resumo" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">O gene LMNA codifica a lâmina A/C, com importante papel na manutenção da coesão nuclear e organização da cromatina. Mutações neste gene estão geralmente associadas a doenças denominadas laminopatias. As manifestações cardíacas primárias destas mutações são miocardiopatia dilatada e defeitos da condução intracardíaca. Algumas mutações, associadas a lipodistrofia, mas não cardiomiopatia, estão também associadas a alterações metabólicas, como diabetes ou dislipidemia grave. Assim, descrevemos um novo fenótipo associado a uma mutação no exão 11 do gene LMNA: miocardiopatia hipertrófica, bloqueio auriculoventricular, dislipidemia grave e diabetes.</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Apresentamos a situação clínica de uma doente de 64 anos de idade, com miocardiopatia hipertrófica e mutação patogénica identificada no exão 11 do gene LMNA (c.1718C>T, Ser573Leu). A doente apresentou-se com hipertrofia ventricular grave sintomática, obstrutiva, refratária à terapêutica médica. Foi submetida a ablação septal por álcool e, posteriormente, a miectomia cirúrgica. Foi também diagnosticada dislipidemia grave, diabetes e obesidade, cumprindo os critérios para síndrome metabólica. Não foi identificada nenhuma outra característica fenotípica associada a mutações no gene LMNA. A doente foi ainda submetida a terapêutica de ressincronização cardíaca após o desenvolvimento de bloqueio auriculoventricular completo, sem causa aparente, na presença de ligeiro compromisso da função sistólica ventricular.</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">A correlação de mutações no gene LMNA com diferentes fenótipos é complexa e ainda não completamente compreendida, englobando um largo espectro de gravidade clínica.</p></span>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:19 [ 0 => array:3 [ "identificador" => "bib0100" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Structural organization of the human gene encoding nuclear lamin A and nuclear lamin C" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "F. Lin" 1 => "H.J. Worman" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Biol Chem" "fecha" => "1993" "volumen" => "268" "paginaInicial" => "16321" "paginaFinal" => "16326" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8344919" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0105" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Nuclear lamins, diseases and aging" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "A. Mattout" 1 => "T. Dechat" 2 => "S.A. Adam" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ceb.2006.03.007" "Revista" => array:6 [ "tituloSerie" => "Curr Opin Cell Biol" "fecha" => "2006" "volumen" => "18" "paginaInicial" => "335" "paginaFinal" => "341" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16632339" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0110" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Extreme variability of skeletal and cardiac muscle involvement in patients with mutations in exon 11 of the lamin A/C gene" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "E. Mercuri" 1 => "S.C. Brown" 2 => "P. Nihoyannopoulos" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/mus.20293" "Revista" => array:6 [ "tituloSerie" => "Muscle Nerve" "fecha" => "2005" "volumen" => "31" "paginaInicial" => "602" "paginaFinal" => "609" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15770669" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0115" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A novel phenotypic expression associated with a new mutation in LMNA gene, characterized by partial lipodystrophy, insulin resistance, aortic stenosis and hypertrophic cardiomyopathy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "D. Araújo-Vilar" 1 => "J. Lado-Abeal" 2 => "F. Palos-Paz" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Clin Endocrinol" "fecha" => "2008" "volumen" => "69" "paginaInicial" => "61" "paginaFinal" => "68" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0120" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Genetic basis of lipodystrophies and management of metabolic complications" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A.K. Agarwal" 1 => "A. Garg" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1146/annurev.med.57.022605.114424" "Revista" => array:6 [ "tituloSerie" => "Annu Rev Med" "fecha" => "2006" "volumen" => "57" "paginaInicial" => "297" "paginaFinal" => "311" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16409151" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0125" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "High incidence of sudden death with conduction system and myocardial disease due to lamins A and C gene mutation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "H.M. Mecane" 1 => "G. Bonne" 2 => "S. Varnous" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Pacing Clin Electrophysiol" "fecha" => "2000" "volumen" => "23" "paginaInicial" => "1661" "paginaFinal" => "1666" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11138304" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0130" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The role of Lamin A/C mutations in Danish patients with idiopathic dilated cardiomyopathy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "D.V. Moller" 1 => "T.T. Pham" 2 => "F. Gustafsson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/eurjhf/hfp134" "Revista" => array:6 [ "tituloSerie" => "Eur J Heart Fail" "fecha" => "2009" "volumen" => "11" "paginaInicial" => "1031" "paginaFinal" => "1035" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19875404" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0135" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "e1–5" "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Laminopathies: a Pandora's box of heart failure, bradyarrhythmias and sudden death" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "N. Cabanelas" 1 => "V. Paulo Martins" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.repc.2014.08.007" "Revista" => array:5 [ "tituloSerie" => "Rev Port Cardiol" "fecha" => "2015" "volumen" => "34" "paginaInicial" => "139" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25656816" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0140" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A new clinical condition linked to a novel mutation in lamins A and C with generalized lipoatrophy, insulin-resistant diabetes, disseminated leukomelanodermic papules, liver steatosis, and cardiomyopathy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "F. Caux" 1 => "E. Dubosclard" 2 => "O. Lascols" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1210/jc.2002-021506" "Revista" => array:6 [ "tituloSerie" => "J Clin Endocrinol Metab" "fecha" => "2003" "volumen" => "88" "paginaInicial" => "1006" "paginaFinal" => "1013" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12629077" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0145" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mutations in the Lamin A/C gene mimic arrhythmogenic right ventricular cardiomyopathy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "G. Quarta" 1 => "P. Syrris" 2 => "M. Ashworth" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/eurheartj/ehr451" "Revista" => array:6 [ "tituloSerie" => "Eur Heart J" "fecha" => "2012" "volumen" => "33" "paginaInicial" => "1128" "paginaFinal" => "1136" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22199124" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0150" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Phenotypic diversity in patients with lipodystrophy associated with LMNA mutations" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "P.B. Mory" 1 => "F. Crispim" 2 => "M.B.S. Freire" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1530/EJE-12-0268" "Revista" => array:6 [ "tituloSerie" => "Eur J Endocrinol" "fecha" => "2012" "volumen" => "167" "paginaInicial" => "423" "paginaFinal" => "431" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22700598" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0155" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Multisystem dystrophy syndrome due to novel missense mutations in the amino-terminal head and alpha-helical rod domains of the lamin A/C gene" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A. Garg" 1 => "R.A. Speckman" 2 => "A.M. Bowcock" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Am J Med" "fecha" => "2002" "volumen" => "112" "paginaInicial" => "549" "paginaFinal" => "555" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12015247" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0160" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lamin A/C mutations with lipodystrophy, cardiac abnormalities, and muscular dystrophy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "A.J. Van der Kooi" 1 => "G. Bonne" 2 => "N. Eymard" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Neurology" "fecha" => "2002" "volumen" => "59" "paginaInicial" => "620" "paginaFinal" => "623" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12196663" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0165" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Identification of mutations in the gene encoding lamins A/C in autosomal dominant limb girdle muscular dystrophy with atrioventricular conduction disturbances (LGMD1B)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "A. Muchir" 1 => "G. Bonner" 2 => "A.J. van der Kooi" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Hum Mol Genet" "fecha" => "2000" "volumen" => "9" "paginaInicial" => "1453" "paginaFinal" => "1459" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10814726" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0170" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "How do mutations in lamins A and C cause diseases?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "H.J. Worman" 1 => "J.C. Courvalin" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Clin Invest" "fecha" => "1998" "volumen" => "113" "paginaInicial" => "2567" "paginaFinal" => "2580" ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0175" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Improvement in clinical outcomes with biventricular versus right ventricular pacing: the BLOCK HF study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "A.B. Curtis" 1 => "S.J. Worley" 2 => "E.S. Chung" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jacc.2016.02.051" "Revista" => array:6 [ "tituloSerie" => "J Am Coll Cardiol" "fecha" => "2016" "volumen" => "67" "paginaInicial" => "2148" "paginaFinal" => "2157" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27151347" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0180" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Natural history of dilated cardiomyopathy due to lamin A/C gene mutations" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "M.R. Taylor" 1 => "P.R. Fain" 2 => "G. Sinagra" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Am Coll Cardiol" "fecha" => "2003" "volumen" => "41" "paginaInicial" => "771" "paginaFinal" => "780" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12628721" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0185" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A homozygous mutation in the lamin A/C gene associated with a novel syndrome of arthropathy, tendinous calcinosis, and progeroid features" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "H. Van Esch" 1 => "A.K. Agarwal" 2 => "P. Debeer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1210/jc.2005-1297" "Revista" => array:6 [ "tituloSerie" => "J Clin Endocrinol Metab" "fecha" => "2006" "volumen" => "91" "paginaInicial" => "517" "paginaFinal" => "521" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16278265" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0190" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Novel LMNA mutations seen in patients with familial partial lipodystrophy subtype 2 (FPLD2; MIM 151660)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "M. Lanktree" 1 => "H. Cao" 2 => "S.W. Rabkin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1399-0004.2007.00740.x" "Revista" => array:6 [ "tituloSerie" => "Clin Genet" "fecha" => "2007" "volumen" => "71" "paginaInicial" => "183" "paginaFinal" => "186" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17250669" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack299798" "titulo" => "Acknowledgments" "texto" => "<p id="par0100" class="elsevierStylePara elsevierViewall">The authors thank Dr. Gabriel Miltenberger Miltényi (MD, PhD, molecular geneticist), for his contribution to the literature review of the mutation reported in this case.</p>" "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/08702551/0000003600000009/v1_201709150927/S0870255117305590/v1_201709150927/en/main.assets" "Apartado" => array:4 [ "identificador" => "29263" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Casos Clínicos" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/08702551/0000003600000009/v1_201709150927/S0870255117305590/v1_201709150927/en/main.pdf?idApp=UINPBA00004E&text.app=https://revportcardiol.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255117305590?idApp=UINPBA00004E" ]
| Ano/Mês | Html | Total | |
|---|---|---|---|
| 2024 Novembro | 8 | 5 | 13 |
| 2024 Outubro | 36 | 28 | 64 |
| 2024 Setembro | 45 | 25 | 70 |
| 2024 Agosto | 35 | 30 | 65 |
| 2024 Julho | 37 | 31 | 68 |
| 2024 Junho | 45 | 30 | 75 |
| 2024 Maio | 37 | 20 | 57 |
| 2024 Abril | 28 | 36 | 64 |
| 2024 Maro | 38 | 25 | 63 |
| 2024 Fevereiro | 35 | 16 | 51 |
| 2024 Janeiro | 29 | 20 | 49 |
| 2023 Dezembro | 27 | 25 | 52 |
| 2023 Novembro | 33 | 35 | 68 |
| 2023 Outubro | 16 | 19 | 35 |
| 2023 Setembro | 32 | 20 | 52 |
| 2023 Agosto | 18 | 22 | 40 |
| 2023 Julho | 18 | 7 | 25 |
| 2023 Junho | 31 | 17 | 48 |
| 2023 Maio | 33 | 27 | 60 |
| 2023 Abril | 22 | 2 | 24 |
| 2023 Maro | 23 | 23 | 46 |
| 2023 Fevereiro | 26 | 22 | 48 |
| 2023 Janeiro | 18 | 9 | 27 |
| 2022 Dezembro | 24 | 20 | 44 |
| 2022 Novembro | 35 | 35 | 70 |
| 2022 Outubro | 25 | 18 | 43 |
| 2022 Setembro | 28 | 40 | 68 |
| 2022 Agosto | 20 | 29 | 49 |
| 2022 Julho | 41 | 36 | 77 |
| 2022 Junho | 32 | 32 | 64 |
| 2022 Maio | 20 | 23 | 43 |
| 2022 Abril | 41 | 48 | 89 |
| 2022 Maro | 34 | 61 | 95 |
| 2022 Fevereiro | 26 | 39 | 65 |
| 2022 Janeiro | 18 | 39 | 57 |
| 2021 Dezembro | 22 | 30 | 52 |
| 2021 Novembro | 26 | 34 | 60 |
| 2021 Outubro | 22 | 47 | 69 |
| 2021 Setembro | 32 | 33 | 65 |
| 2021 Agosto | 39 | 28 | 67 |
| 2021 Julho | 18 | 22 | 40 |
| 2021 Junho | 41 | 34 | 75 |
| 2021 Maio | 37 | 36 | 73 |
| 2021 Abril | 40 | 55 | 95 |
| 2021 Maro | 55 | 32 | 87 |
| 2021 Fevereiro | 61 | 17 | 78 |
| 2021 Janeiro | 26 | 14 | 40 |
| 2020 Dezembro | 40 | 4 | 44 |
| 2020 Novembro | 22 | 18 | 40 |
| 2020 Outubro | 11 | 10 | 21 |
| 2020 Setembro | 57 | 14 | 71 |
| 2020 Agosto | 17 | 5 | 22 |
| 2020 Julho | 31 | 6 | 37 |
| 2020 Junho | 26 | 22 | 48 |
| 2020 Maio | 30 | 5 | 35 |
| 2020 Abril | 33 | 15 | 48 |
| 2020 Maro | 33 | 16 | 49 |
| 2020 Fevereiro | 45 | 21 | 66 |
| 2020 Janeiro | 19 | 8 | 27 |
| 2019 Dezembro | 40 | 8 | 48 |
| 2019 Novembro | 40 | 15 | 55 |
| 2019 Outubro | 57 | 13 | 70 |
| 2019 Setembro | 19 | 8 | 27 |
| 2019 Agosto | 39 | 10 | 49 |
| 2019 Julho | 35 | 10 | 45 |
| 2019 Junho | 33 | 20 | 53 |
| 2019 Maio | 38 | 21 | 59 |
| 2019 Abril | 19 | 16 | 35 |
| 2019 Maro | 19 | 14 | 33 |
| 2019 Fevereiro | 20 | 18 | 38 |
| 2019 Janeiro | 33 | 7 | 40 |
| 2018 Dezembro | 40 | 16 | 56 |
| 2018 Novembro | 64 | 7 | 71 |
| 2018 Outubro | 150 | 16 | 166 |
| 2018 Setembro | 64 | 13 | 77 |
| 2018 Agosto | 39 | 10 | 49 |
| 2018 Julho | 25 | 8 | 33 |
| 2018 Junho | 53 | 8 | 61 |
| 2018 Maio | 49 | 7 | 56 |
| 2018 Abril | 66 | 10 | 76 |
| 2018 Maro | 82 | 17 | 99 |
| 2018 Fevereiro | 28 | 10 | 38 |
| 2018 Janeiro | 25 | 6 | 31 |
| 2017 Dezembro | 47 | 24 | 71 |
| 2017 Novembro | 62 | 18 | 80 |
| 2017 Outubro | 73 | 52 | 125 |
| 2017 Setembro | 50 | 57 | 107 |
Mostrar tudo
