Rebeca Lorca1, Juan Gómez2, María Martín3, Rubén Cabanillas4, Juan Calvo5, Víctor León2, Isaac Pascual2, César Morís6, Eliecer Coto6, José Julián R Reguero7. 1. Unidad de Cardiopatías Familiares, Departamento de Cardiología y Genética Molecular, Hospital Universitario Central de Asturias (HUCA), Oviedo, Asturias, Spain. Electronic address: lorcarebeca@gmail.com. 2. Unidad de Cardiopatías Familiares, Departamento de Cardiología y Genética Molecular, Hospital Universitario Central de Asturias (HUCA), Oviedo, Asturias, Spain. 3. Unidad de Cardiopatías Familiares, Departamento de Cardiología y Genética Molecular, Hospital Universitario Central de Asturias (HUCA), Oviedo, Asturias, Spain; Departamento de Biología Funcional, Universidad de Oviedo, Oviedo, Asturias, Spain. 4. Instituto de Medicina Oncológica y Molecular de Asturias (IMOMA), Oviedo, Asturias, Spain. 5. Departamento de Radiología, Hospital Universitario Central de Asturias (HUCA), Oviedo, Asturias, Spain. 6. Unidad de Cardiopatías Familiares, Departamento de Cardiología y Genética Molecular, Hospital Universitario Central de Asturias (HUCA), Oviedo, Asturias, Spain; Instituto de Investigación Sanitaria del Principado de Asturias (IISPA), Oviedo, Asturias, Spain; Departamento de Medicina, Universidad de Oviedo, Oviedo, Asturias, Spain. 7. Unidad de Cardiopatías Familiares, Departamento de Cardiología y Genética Molecular, Hospital Universitario Central de Asturias (HUCA), Oviedo, Asturias, Spain; Instituto de Investigación Sanitaria del Principado de Asturias (IISPA), Oviedo, Asturias, Spain.
Abstract
INTRODUCTION AND OBJECTIVES: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease. The current challenge relies on the accurate classification of the pathogenicity of the variants. Transthoracic echocardiography (TTE) is recommended at initial evaluation and cardiac magnetic resonance (CMR) imaging should also be considered. We aimed to reappraise the penetrance and clinical expression of the MYBPC3 p.G263* variant. METHODS: Three hundred and eighty-four HCM probands and a control cohort of 450 individuals were studied for the main sarcomere genes by next-generation sequencing. All MYBPC3 p.G263* carriers were identified and family screening was performed. Clinical information was recorded retrospectively before 2015 and prospectively thereafter. Extra effort was invested in performing CMR in all carriers, despite TTE results. RESULTS: Thirteen HCM probands and none of the controls were carriers of the MYBPC3 p.G263* pathogenic variant (according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology). A total of 39 carriers were identified with family screening. Most patients with HCM were asymptomatic at the time of diagnosis and showed late-onset disease. Despite having a relatively benign course in the young, late HCM-related complications could occur. Penetrance was around 70% when evaluated by TTE and was 87.2% with TTE plus CMR. Penetrance was age-dependent, reaching 100% in carriers older than 55 years. CONCLUSIONS: MYBPC3 p.G263* shares with most truncating pathogenic variants in this gene a late onset, relatively benign clinical course in the young, and high penetrance. Cardiac magnetic resonance could be a useful tool to evaluate carriers despite TTE results.
INTRODUCTION AND OBJECTIVES:Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease. The current challenge relies on the accurate classification of the pathogenicity of the variants. Transthoracic echocardiography (TTE) is recommended at initial evaluation and cardiac magnetic resonance (CMR) imaging should also be considered. We aimed to reappraise the penetrance and clinical expression of the MYBPC3p.G263* variant. METHODS: Three hundred and eighty-four HCM probands and a control cohort of 450 individuals were studied for the main sarcomere genes by next-generation sequencing. All MYBPC3p.G263* carriers were identified and family screening was performed. Clinical information was recorded retrospectively before 2015 and prospectively thereafter. Extra effort was invested in performing CMR in all carriers, despite TTE results. RESULTS: Thirteen HCM probands and none of the controls were carriers of the MYBPC3p.G263* pathogenic variant (according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology). A total of 39 carriers were identified with family screening. Most patients with HCM were asymptomatic at the time of diagnosis and showed late-onset disease. Despite having a relatively benign course in the young, late HCM-related complications could occur. Penetrance was around 70% when evaluated by TTE and was 87.2% with TTE plus CMR. Penetrance was age-dependent, reaching 100% in carriers older than 55 years. CONCLUSIONS:MYBPC3p.G263* shares with most truncating pathogenic variants in this gene a late onset, relatively benign clinical course in the young, and high penetrance. Cardiac magnetic resonance could be a useful tool to evaluate carriers despite TTE results.
Authors: Ella Field; Gabrielle Norrish; Vanessa Acquaah; Kathleen Dady; Marcos Nicolas Cicerchia; Juan Pablo Ochoa; Petros Syrris; Karen McLeod; Ruth McGowan; Hannah Fell; Luis R Lopes; Elena Cervi; Juan Pablo Pablo Kaski Journal: J Med Genet Date: 2021-08-16 Impact factor: 5.941
Authors: Irene Méndez; Ana Isabel Fernández; Maria Ángeles Espinosa; Sofía Cuenca; Rebeca Lorca; José Fernando Rodríguez; Maria Tamargo; Marta García-Montero; Cristina Gómez; Silvia Vilches; Nélida Vázquez; Reyes Álvarez; Constancio Medrano; Raquel Yotti; Francisco Fernández-Avilés; Javier Bermejo Journal: Open Heart Date: 2021-09