María Sabater-Molina1, Daniel Saura2, Esperanza García-Molina Sáez3, Josefa González-Carrillo2, Luis Polo4, Inmaculada Pérez-Sánchez3, María Del Carmen Olmo2, María José Oliva-Sandoval2, Roberto Barriales-Villa5, Pablo Carbonell6, Domigo Pascual-Figal2, Juan R Gimeno2. 1. Unidad de Cardiopatías Hereditarias, Hospital Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain. Electronic address: mariasm79es@hotmail.com. 2. Departamento de Cardiología, Hospital Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain. 3. Unidad de Cardiopatías Hereditarias, Hospital Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain. 4. Departamento de Patología, Hospital Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain. 5. Unidad de Cardiopatías Hereditarias, Complexo Hospitalario Universitario A Coruña, A Coruña, Spain. 6. Centro de Bioquímica y Genética Clínica, Hospital Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain.
Abstract
INTRODUCTION AND OBJECTIVES: Mutations in MYBPC3 are the cause of hypertrophic cardiomyopathy (HCM). Although most lead to a truncating protein, the severity of the phenotype differs. We describe the clinical phenotype of a novel MYBPC3 mutation, p.Pro108Alafs*9, present in 13 families from southern Spain and compare it with the most prevalent MYBPC3 mutation in this region (c.2308+1 G>A). METHODS: We studied 107 relatives of 13 index cases diagnosed as HCM carriers of the p.Pro108Alafs*9 mutation. Pedigree analysis, clinical evaluation, and genotyping were performed. RESULTS: A total of 54 carriers of p.Pro108Alafs*9 were identified, of whom 39 had HCM. There were 5 cases of sudden death in the 13 families. Disease penetrance was greater as age increased and HCM patients were more frequently male and developed disease earlier than female patients. The phenotype was similar in p.Pro108Alafs*9 and in c.2308+1 G>A, but differences were found in several risk factors and in survival. There was a trend toward a higher left ventricular mass in p.Pro108Alafs*9 vs c.2308+1G>A. Cardiac magnetic resonance revealed a similar extent and pattern of fibrosis. CONCLUSIONS: The p.Pro108Alafs*9 mutation is associated with HCM, high penetrance, and disease onset in middle age.
INTRODUCTION AND OBJECTIVES: Mutations in MYBPC3 are the cause of hypertrophic cardiomyopathy (HCM). Although most lead to a truncating protein, the severity of the phenotype differs. We describe the clinical phenotype of a novel MYBPC3 mutation, p.Pro108Alafs*9, present in 13 families from southern Spain and compare it with the most prevalent MYBPC3 mutation in this region (c.2308+1 G>A). METHODS: We studied 107 relatives of 13 index cases diagnosed as HCM carriers of the p.Pro108Alafs*9 mutation. Pedigree analysis, clinical evaluation, and genotyping were performed. RESULTS: A total of 54 carriers of p.Pro108Alafs*9 were identified, of whom 39 had HCM. There were 5 cases of sudden death in the 13 families. Disease penetrance was greater as age increased and HCM patients were more frequently male and developed disease earlier than female patients. The phenotype was similar in p.Pro108Alafs*9 and in c.2308+1 G>A, but differences were found in several risk factors and in survival. There was a trend toward a higher left ventricular mass in p.Pro108Alafs*9 vs c.2308+1G>A. Cardiac magnetic resonance revealed a similar extent and pattern of fibrosis. CONCLUSIONS: The p.Pro108Alafs*9 mutation is associated with HCM, high penetrance, and disease onset in middle age.
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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